CA3015432A1 - Ambrisentan for use in the treatment of acute renal failure - Google Patents
Ambrisentan for use in the treatment of acute renal failure Download PDFInfo
- Publication number
- CA3015432A1 CA3015432A1 CA3015432A CA3015432A CA3015432A1 CA 3015432 A1 CA3015432 A1 CA 3015432A1 CA 3015432 A CA3015432 A CA 3015432A CA 3015432 A CA3015432 A CA 3015432A CA 3015432 A1 CA3015432 A1 CA 3015432A1
- Authority
- CA
- Canada
- Prior art keywords
- ambrisentan
- administered
- subject
- maintained below
- plasma levels
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical compound O([C@@H](C(OC)(C=1C=CC=CC=1)C=1C=CC=CC=1)C(O)=O)C1=NC(C)=CC(C)=N1 OUJTZYPIHDYQMC-LJQANCHMSA-N 0.000 title claims description 636
- 229960002414 ambrisentan Drugs 0.000 title claims description 632
- 238000011282 treatment Methods 0.000 title claims description 79
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims description 58
- 208000033626 Renal failure acute Diseases 0.000 title claims description 58
- 201000011040 acute kidney failure Diseases 0.000 title claims description 58
- 208000012998 acute renal failure Diseases 0.000 title claims description 23
- 239000000203 mixture Substances 0.000 claims description 196
- 239000007788 liquid Substances 0.000 claims description 160
- 230000036470 plasma concentration Effects 0.000 claims description 139
- 210000003734 kidney Anatomy 0.000 claims description 103
- 238000000034 method Methods 0.000 claims description 75
- 230000003907 kidney function Effects 0.000 claims description 73
- 206010047139 Vasoconstriction Diseases 0.000 claims description 44
- 230000025033 vasoconstriction Effects 0.000 claims description 44
- 238000002054 transplantation Methods 0.000 claims description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 201000006370 kidney failure Diseases 0.000 claims description 27
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 239000000872 buffer Substances 0.000 claims description 21
- 210000004185 liver Anatomy 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 21
- 208000004990 Cardiorenal syndrome Diseases 0.000 claims description 20
- 230000002792 vascular Effects 0.000 claims description 20
- 206010003445 Ascites Diseases 0.000 claims description 19
- 208000021709 Delayed Graft Function Diseases 0.000 claims description 19
- 238000007675 cardiac surgery Methods 0.000 claims description 19
- 201000011200 hepatorenal syndrome Diseases 0.000 claims description 19
- 231100000417 nephrotoxicity Toxicity 0.000 claims description 19
- 206010029155 Nephropathy toxic Diseases 0.000 claims description 18
- 230000007694 nephrotoxicity Effects 0.000 claims description 18
- 206010021036 Hyponatraemia Diseases 0.000 claims description 16
- 229940122739 Calcineurin inhibitor Drugs 0.000 claims description 15
- 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 claims description 15
- 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 claims description 15
- 238000007920 subcutaneous administration Methods 0.000 claims description 15
- 230000006872 improvement Effects 0.000 claims description 8
- 238000001990 intravenous administration Methods 0.000 claims description 8
- 238000004321 preservation Methods 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 230000009977 dual effect Effects 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 4
- 239000003708 ampul Substances 0.000 claims description 4
- 229940071643 prefilled syringe Drugs 0.000 claims description 4
- 230000003111 delayed effect Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 102220240796 rs553605556 Human genes 0.000 abstract 2
- 229960000074 biopharmaceutical Drugs 0.000 abstract 1
- 230000008520 organization Effects 0.000 abstract 1
- 239000005557 antagonist Substances 0.000 description 39
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 38
- 239000000243 solution Substances 0.000 description 34
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 31
- 239000002308 endothelin receptor antagonist Substances 0.000 description 31
- 210000002966 serum Anatomy 0.000 description 27
- 108050009340 Endothelin Proteins 0.000 description 22
- 102000002045 Endothelin Human genes 0.000 description 22
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 22
- 230000002485 urinary effect Effects 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 210000002700 urine Anatomy 0.000 description 21
- 208000035475 disorder Diseases 0.000 description 20
- 238000009472 formulation Methods 0.000 description 20
- 229940109239 creatinine Drugs 0.000 description 19
- 230000003247 decreasing effect Effects 0.000 description 17
- 210000004369 blood Anatomy 0.000 description 16
- 239000008280 blood Substances 0.000 description 16
- 239000011734 sodium Substances 0.000 description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 230000002265 prevention Effects 0.000 description 14
- 230000009467 reduction Effects 0.000 description 14
- 229910052708 sodium Inorganic materials 0.000 description 14
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 230000007423 decrease Effects 0.000 description 12
- 230000024924 glomerular filtration Effects 0.000 description 12
- 230000008327 renal blood flow Effects 0.000 description 12
- 230000010410 reperfusion Effects 0.000 description 12
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 210000002381 plasma Anatomy 0.000 description 10
- 102000012192 Cystatin C Human genes 0.000 description 9
- 108010061642 Cystatin C Proteins 0.000 description 9
- 238000010606 normalization Methods 0.000 description 9
- 238000007911 parenteral administration Methods 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 8
- 229950010993 atrasentan Drugs 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- FJHHZXWJVIEFGJ-UHFFFAOYSA-N N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2OC=NN=2)C=C1 FJHHZXWJVIEFGJ-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000002980 postoperative effect Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- 229950003684 zibotentan Drugs 0.000 description 6
- 101800004490 Endothelin-1 Proteins 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 239000002934 diuretic Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 102000017930 EDNRB Human genes 0.000 description 4
- 206010014418 Electrolyte imbalance Diseases 0.000 description 4
- 102100033902 Endothelin-1 Human genes 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 208000004880 Polyuria Diseases 0.000 description 4
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 229940039231 contrast media Drugs 0.000 description 4
- 239000002872 contrast media Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 229940090243 letairis Drugs 0.000 description 4
- 239000012669 liquid formulation Substances 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 230000036284 oxygen consumption Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 229960001967 tacrolimus Drugs 0.000 description 4
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 108010090557 Endothelin B Receptor Proteins 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- 206010019663 Hepatic failure Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000036765 blood level Effects 0.000 description 3
- 229940046731 calcineurin inhibitors Drugs 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 235000019800 disodium phosphate Nutrition 0.000 description 3
- 230000035619 diuresis Effects 0.000 description 3
- 230000001882 diuretic effect Effects 0.000 description 3
- 229940030606 diuretics Drugs 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 208000007903 liver failure Diseases 0.000 description 3
- 231100000835 liver failure Toxicity 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000003182 parenteral nutrition solution Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 208000007788 Acute Liver Failure Diseases 0.000 description 2
- 206010000804 Acute hepatic failure Diseases 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 229930105110 Cyclosporin A Natural products 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 102000010180 Endothelin receptor Human genes 0.000 description 2
- 108050001739 Endothelin receptor Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 201000001431 Hyperuricemia Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000008156 Ringer's lactate solution Substances 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 231100000836 acute liver failure Toxicity 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229960003065 bosentan Drugs 0.000 description 2
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229960001484 edetic acid Drugs 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000000004 hemodynamic effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 208000037906 ischaemic injury Diseases 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- JGCMEBMXRHSZKX-UHFFFAOYSA-N macitentan Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 JGCMEBMXRHSZKX-UHFFFAOYSA-N 0.000 description 2
- 229960001039 macitentan Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 235000019799 monosodium phosphate Nutrition 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 229960003330 pentetic acid Drugs 0.000 description 2
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 2
- 229960002578 sitaxentan Drugs 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000006442 vascular tone Effects 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- VYCMAAOURFJIHD-PJNXIOHISA-N BQ 123 Chemical compound N1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](CC(O)=O)NC(=O)[C@H]1CC1=CNC2=CC=CC=C12 VYCMAAOURFJIHD-PJNXIOHISA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 102000017914 EDNRA Human genes 0.000 description 1
- 108010090549 Endothelin A Receptor Proteins 0.000 description 1
- 102100040611 Endothelin receptor type B Human genes 0.000 description 1
- 101710194572 Endothelin receptor type B Proteins 0.000 description 1
- 102400000686 Endothelin-1 Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000967299 Homo sapiens Endothelin receptor type B Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108700042768 University of Wisconsin-lactobionate solution Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037058 blood plasma level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229940067596 butylparaben Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- QTDIPNAZPWHKMZ-UHFFFAOYSA-P calcium;2-[4,7-bis(carboxylatomethyl)-10-(2-oxidopropyl)-1,4,7,10-tetrazoniacyclododec-1-yl]acetate;hydron Chemical compound [H+].[Ca+2].CC([O-])C[NH+]1CC[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC1 QTDIPNAZPWHKMZ-UHFFFAOYSA-P 0.000 description 1
- SHWNNYZBHZIQQV-UHFFFAOYSA-L calcium;disodium;2-[2-[bis(carboxylatomethyl)azaniumyl]ethyl-(carboxylatomethyl)azaniumyl]acetate Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-L 0.000 description 1
- 229960004858 calteridol Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- FEJVSJIALLTFRP-LJQANCHMSA-N darusentan Chemical compound COC1=CC(OC)=NC(O[C@H](C(O)=O)C(OC)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 FEJVSJIALLTFRP-LJQANCHMSA-N 0.000 description 1
- 229950008833 darusentan Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002526 disodium citrate Substances 0.000 description 1
- 235000019262 disodium citrate Nutrition 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 239000000815 hypotonic solution Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000005977 kidney dysfunction Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- TUYWTLTWNJOZNY-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C2=NNN=N2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 TUYWTLTWNJOZNY-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 210000002796 renal vein Anatomy 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000019980 sodium acid phosphate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 229950000584 tezosentan Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940001496 tribasic sodium phosphate Drugs 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 235000019263 trisodium citrate Nutrition 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 229960002569 versetamide Drugs 0.000 description 1
- AXFGWXLCWCNPHP-UHFFFAOYSA-N versetamide Chemical compound COCCNC(=O)CN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC(=O)NCCOC AXFGWXLCWCNPHP-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/70—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving creatine or creatinine
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662310221P | 2016-03-18 | 2016-03-18 | |
| US62/310,221 | 2016-03-18 | ||
| EP16166046.9 | 2016-04-19 | ||
| EP16166046.9A EP3235496A1 (en) | 2016-04-19 | 2016-04-19 | Treatment of acute renal failure |
| US201662437949P | 2016-12-22 | 2016-12-22 | |
| US62/437,949 | 2016-12-22 | ||
| PCT/EP2017/056476 WO2017158199A1 (en) | 2016-03-18 | 2017-03-20 | Ambrisentan for use in the treatment of acute renal failure |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3015432A1 true CA3015432A1 (en) | 2017-09-21 |
Family
ID=55808404
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3015432A Pending CA3015432A1 (en) | 2016-03-18 | 2017-03-20 | Ambrisentan for use in the treatment of acute renal failure |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US10870021B2 (enExample) |
| EP (3) | EP3235496A1 (enExample) |
| JP (1) | JP7237362B2 (enExample) |
| KR (1) | KR20180121539A (enExample) |
| CN (1) | CN109069443A (enExample) |
| AU (1) | AU2017235618B2 (enExample) |
| BR (1) | BR112018067602A2 (enExample) |
| CA (1) | CA3015432A1 (enExample) |
| CL (1) | CL2018002638A1 (enExample) |
| DK (1) | DK3429566T3 (enExample) |
| ES (2) | ES2966638T3 (enExample) |
| HK (1) | HK1259616A1 (enExample) |
| IL (1) | IL261457B (enExample) |
| MX (1) | MX374534B (enExample) |
| SG (1) | SG11201808009SA (enExample) |
| WO (1) | WO2017158199A1 (enExample) |
| ZA (1) | ZA201805562B (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3639827A1 (en) | 2018-10-19 | 2020-04-22 | Noorik Biopharmaceuticals AG | Use of ambrisentan for the treatment of portal hypertension and cirrhosis |
| EP4142731A1 (en) * | 2020-04-28 | 2023-03-08 | Noorik Biopharmaceuticals AG | Treatment of pulmonary complications of coronavirus infections |
| WO2021219691A1 (en) * | 2020-04-29 | 2021-11-04 | Astrazeneca Ab | Dapagliflozin and ambrisentan for the prevention and treatment of covid-19 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19533023B4 (de) | 1994-10-14 | 2007-05-16 | Basf Ag | Neue Carbonsäurederivate, ihre Herstellung und Verwendung |
| CA2695259C (en) * | 2007-07-31 | 2016-05-24 | Gilead Colorado, Inc. | Metabolites and derivatives of ambrisentan |
| US9255931B2 (en) * | 2010-06-24 | 2016-02-09 | Morehouse School Of Medicine | Method and compositions for the treatment and detection of endothelin-1 related kidney diseases |
| KR20140130705A (ko) * | 2012-02-29 | 2014-11-11 | 도레이 카부시키가이샤 | 체강액 저류 억제제 |
| CA2901922A1 (en) * | 2013-03-08 | 2014-09-12 | Abbvie Inc. | Methods of treating acute kidney injury |
| EP2988770A4 (en) * | 2013-04-26 | 2016-12-14 | La Jolla Pharma Co | COMPOSITIONS AND METHOD FOR TREATING KIDNEY FAILURES |
| WO2015069839A1 (en) * | 2013-11-06 | 2015-05-14 | Gilead Sciences, Inc. | Combination therapy for treating pulmonary hypertension |
-
2016
- 2016-04-19 EP EP16166046.9A patent/EP3235496A1/en not_active Withdrawn
-
2017
- 2017-03-20 BR BR112018067602A patent/BR112018067602A2/pt not_active Application Discontinuation
- 2017-03-20 MX MX2018011222A patent/MX374534B/es active IP Right Grant
- 2017-03-20 DK DK17711211.7T patent/DK3429566T3/da active
- 2017-03-20 EP EP17711211.7A patent/EP3429566B1/en active Active
- 2017-03-20 HK HK19101803.4A patent/HK1259616A1/zh unknown
- 2017-03-20 EP EP20175547.7A patent/EP3878439B1/en active Active
- 2017-03-20 US US16/084,340 patent/US10870021B2/en active Active
- 2017-03-20 ES ES20175547T patent/ES2966638T3/es active Active
- 2017-03-20 ES ES17711211T patent/ES2856960T3/es active Active
- 2017-03-20 SG SG11201808009SA patent/SG11201808009SA/en unknown
- 2017-03-20 CN CN201780017563.3A patent/CN109069443A/zh active Pending
- 2017-03-20 KR KR1020187026495A patent/KR20180121539A/ko not_active Ceased
- 2017-03-20 CA CA3015432A patent/CA3015432A1/en active Pending
- 2017-03-20 JP JP2019500021A patent/JP7237362B2/ja active Active
- 2017-03-20 AU AU2017235618A patent/AU2017235618B2/en active Active
- 2017-03-20 WO PCT/EP2017/056476 patent/WO2017158199A1/en not_active Ceased
-
2018
- 2018-08-21 ZA ZA2018/05562A patent/ZA201805562B/en unknown
- 2018-08-29 IL IL261457A patent/IL261457B/en unknown
- 2018-09-14 CL CL2018002638A patent/CL2018002638A1/es unknown
-
2020
- 2020-10-07 US US17/065,097 patent/US11642307B2/en active Active
-
2023
- 2023-03-31 US US18/129,516 patent/US20230233454A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US10870021B2 (en) | 2020-12-22 |
| AU2017235618A1 (en) | 2018-09-27 |
| IL261457A (en) | 2018-10-31 |
| DK3429566T3 (da) | 2021-03-29 |
| EP3429566A1 (en) | 2019-01-23 |
| US20210046332A1 (en) | 2021-02-18 |
| ZA201805562B (en) | 2019-06-26 |
| SG11201808009SA (en) | 2018-10-30 |
| CL2018002638A1 (es) | 2019-01-18 |
| IL261457B (en) | 2021-09-30 |
| WO2017158199A1 (en) | 2017-09-21 |
| BR112018067602A2 (pt) | 2019-01-08 |
| AU2017235618B2 (en) | 2021-02-25 |
| US20190083820A1 (en) | 2019-03-21 |
| CN109069443A (zh) | 2018-12-21 |
| MX2018011222A (es) | 2019-01-10 |
| EP3878439A1 (en) | 2021-09-15 |
| EP3878439B1 (en) | 2023-10-04 |
| US11642307B2 (en) | 2023-05-09 |
| ES2856960T3 (es) | 2021-09-28 |
| ES2966638T3 (es) | 2024-04-23 |
| MX374534B (es) | 2025-03-06 |
| JP7237362B2 (ja) | 2023-03-13 |
| EP3429566B1 (en) | 2021-01-27 |
| EP3235496A1 (en) | 2017-10-25 |
| KR20180121539A (ko) | 2018-11-07 |
| US20230233454A1 (en) | 2023-07-27 |
| HK1259616A1 (zh) | 2019-12-06 |
| NZ746140A (en) | 2022-03-25 |
| JP2019515942A (ja) | 2019-06-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230233454A1 (en) | Ambrisentan for use in the treatment of acute renal failure | |
| RU2640023C2 (ru) | Жидкий состав | |
| JP7082115B2 (ja) | 異常な新生血管形成を伴う眼疾患を処置するためにニンテダニブを使用する組成物および方法 | |
| US9597398B2 (en) | Formulations of bendamustine | |
| US20090018136A1 (en) | Methods and compositions for the treatment of vascular disease | |
| KR20170141757A (ko) | 테트라하이드로나프티리디닐 프로피온산 유도체 및 이의 용도 | |
| NZ746140B2 (en) | Ambrisentan for use in the treatment of acute renal failure | |
| NZ786075A (en) | Ambrisentan for use in the treatment of acute renal failure | |
| Cousins et al. | Anaesthesia, surgery and renal function: immediate and delayed effects | |
| JP3060287B2 (ja) | アパファントを主薬とする水性点眼剤 | |
| US20230241218A1 (en) | Formulations of bendamustine | |
| WO2020214510A1 (en) | Pharmaceutical formulations containing p2y14 antagonists | |
| Bland-van den Berg | Investigations into the hemodynamic and metabolic effects of fructose 1, 6 diphosphate and prostacyclin in hypovolemic shock | |
| Proteinuria | Renal Transplant Dysfunction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220315 |
|
| EEER | Examination request |
Effective date: 20220315 |
|
| EEER | Examination request |
Effective date: 20220315 |
|
| EEER | Examination request |
Effective date: 20220315 |