US20200376073A1 - Method of treating low blood pressure - Google Patents
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- US20200376073A1 US20200376073A1 US16/725,319 US201916725319A US2020376073A1 US 20200376073 A1 US20200376073 A1 US 20200376073A1 US 201916725319 A US201916725319 A US 201916725319A US 2020376073 A1 US2020376073 A1 US 2020376073A1
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- 238000000034 method Methods 0.000 title claims abstract description 38
- 208000001953 Hypotension Diseases 0.000 title claims abstract description 23
- 208000012866 low blood pressure Diseases 0.000 title description 4
- 101800000733 Angiotensin-2 Proteins 0.000 claims abstract description 21
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 claims abstract description 21
- 229950006323 angiotensin ii Drugs 0.000 claims abstract description 21
- 230000036543 hypotension Effects 0.000 claims abstract description 19
- 206010040070 Septic Shock Diseases 0.000 claims abstract description 12
- 230000036303 septic shock Effects 0.000 claims abstract description 12
- 102000005862 Angiotensin II Human genes 0.000 claims abstract 13
- 230000004872 arterial blood pressure Effects 0.000 claims description 10
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims description 9
- 229960002748 norepinephrine Drugs 0.000 claims description 9
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims description 9
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 claims description 5
- 102000002852 Vasopressins Human genes 0.000 claims description 5
- 108010004977 Vasopressins Proteins 0.000 claims description 5
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 5
- 229960003726 vasopressin Drugs 0.000 claims description 5
- 229960003638 dopamine Drugs 0.000 claims description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 claims description 2
- 229930182837 (R)-adrenaline Natural products 0.000 claims description 2
- 229960005139 epinephrine Drugs 0.000 claims description 2
- 238000001802 infusion Methods 0.000 claims 2
- 238000001990 intravenous administration Methods 0.000 claims 2
- 201000011040 acute kidney failure Diseases 0.000 abstract description 10
- 208000009304 Acute Kidney Injury Diseases 0.000 abstract description 6
- 208000033626 Renal failure acute Diseases 0.000 abstract description 6
- 208000010496 Heart Arrest Diseases 0.000 abstract description 3
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- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
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- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- QMMRCKSBBNJCMR-KMZPNFOHSA-N Angiotensin III Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(C)C)C1=CC=C(O)C=C1 QMMRCKSBBNJCMR-KMZPNFOHSA-N 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 101800000738 Angiotensin-3 Proteins 0.000 description 1
- 102400000348 Angiotensin-3 Human genes 0.000 description 1
- 206010022680 Intestinal ischaemia Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000004535 Mesenteric Ischemia Diseases 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- 206010043087 Tachyphylaxis Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000001943 adrenal medulla Anatomy 0.000 description 1
- 229940124572 antihypotensive agent Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
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- 230000002093 peripheral effect Effects 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/085—Angiotensins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- the present teachings relate to a therapeutic regimen for patients suffering from at least one of septic shock, acute kidney injury, severe hypotension, cardiac arrest, and refractory hypotension.
- Severe sepsis is the leading cause of acute kidney injury (“AKI”) and its incidence is increasing.
- AKI acute kidney injury
- vasopressor e.g. norepinephrine, vasopressin, dopamine
- catecholamines e.g., dopamine, epinephrine, norepinephrine
- Vasopressin which has been used as an adjuvant with cathecholamines, has not been shown to improve outcomes in patients with septic shock. In the subset of patients whose mean arterial pressure cannot be maintained with current vasopressors, septic shock is uniformly fatal.
- the present teachings disclose a method of treating a patient suffering from low blood pressure.
- a method of treating a patient suffering from low blood pressure is provided.
- the patient can suffer from one of septic shock, acute kidney injury, severe hypotension, and refractory hypotension, but not from myocardial infarction.
- the method can comprise administering a therapeutically effective dose of Angiotensin II (“Ang II”) to the patient.
- Ang II Angiotensin II
- the dose of Angiotensin II can be administered at a rate of between about 5 ng/kg/min to about 100 ng/kg/min.
- the dose of Angiotensin II can be administered at a rate of between about 10 ng/kg/min to about 50 ng/kg/min.
- the dose of Angiotensin II can be administered at a rate of between about 20 ng/kg/min to about 40 ng/kg/min.
- the dose administration can last from about 0.25 hours to about 120 hours.
- the dose administration can last from about 1 hour to about 7 hours.
- the dose administration can last from about 2 hour to about 6 hours.
- the dose administration can last from about 3 hours to about 5 hours.
- Ang II is degraded to angiotensin III in a patient, having a half life of a few minutes.
- Ang II is a direct vasoconstrictor by activating angiotensin I receptors, enhancing peripheral noradrenergic neurotransmission, increasing sympathetic discharge (CNS), and releasing catecholamines from the adrenal medulla.
- Ang II Administration of Ang II to patients suffering from at least one of septic shock, acute kidney injury, severe hypotension, cardiac arrest, and refractory hypotension can have adverse side effects, including ischemia, such as, for example, mesenteric ischemia, that damage internal organs.
- ischemia such as, for example, mesenteric ischemia
- the present teachings disclose a therapeutic regimen of Ang II at doses below that where adverse side effects, such as ischemia, are seen.
- the therapeutic regimen of Ang II disclosed in the present teachings can act as an adjuvant and lower the effective doses of other therapies, including administration of vasopressin and catecholamine.
- the therapeutic regimen disclosed herein can be started within, for example, 1 hour, 2 hours, 4 hours, 6 hours, or 12 hours after onset of acute symptoms.
- a dose study was designed to determine the feasibility of Ang II as a treatment for sepsis related hypotension.
- a 20 patient randomized blinded study in the treatment of sepsis related hypotension was proposed. Patients suffering from septic shock receiving >15 mcg/min of norepineprhine are eligible. Patients are randomized to Ang II or norepinephrine in a blinded fashion. There are 10 patients in each arm. Norepinephrine is used as a control instead of a true placebo, because the blood pressure rising effects of Ang II would defeat the blinding intent.
- MAP mean arterial pressure
- Patients are then randomized to a control group or arm, or an interventional group or arm treated with Ang II.
- Patients randomly assigned to the control group are administered with norepinephrine starting at 5 mcg/min, and can be titrated up to 7.5 mcg/mink, and then to 10 mcg/min.
- Patients in the interventional arm are administered Ang II starting at a dose of about 20 ng/kg/min. Additionally, the dose can then be titrated up to about 30 ng/kg/min. Furthermore, the dose can then be titrated up to about 40 ng/kg/min.
- the intervention can last for about 4 hours.
- Each patient in the interventional group is started with the assigned starting dose. After the first hour, if the patient is still requiring standing norepinephrine, the dose of the control and interventional drugs can be increased 50%. After the second hour, if the patient is still requiring a standing dose of norepinephrine, the control and interventional drugs can be increased again to twice the initial dose. At the end of 4 hours, the study drug will be titrated off over 30 minutes.
- Blood pressure of each patient is monitored continuously from about two (2) hours before initiation of the control and interventional drugs for about seven (7) hours after initiation of the control and interventional drugs.
- a method of treating a patient suffering from low blood pressure is provided.
- the patient can suffer from one of septic shock, acute kidney injury, severe hypotension, and refractory hypotension, but not from myocardial infarction.
- the method can comprise administering a therapeutically effective dose of Angiotensin II (“Ang II”) to the patient.
- Ang II Angiotensin II
- the dose of Angiotensin II can be administered at a rate of between about 5 ng/kg/min to about 100 ng/kg/min.
- the dose of Angiotensin II can be administered at a rate of between about 10 ng/kg/min to about 50 ng/kg/min.
- the dose of Angiotensin II can be administered at a rate of between about 20 ng/kg/min to about 40 ng/kg/min.
- the dose administration can last from about 0.25 hours to about 120 hours.
- the dose administration can last from about 1 hour to about 7 hours.
- the dose administration can last from about 2 hour to about 6 hours.
- the dose administration can last from about 3 hours to about 5 hours.
Abstract
A method for treating a patient suffering from one of septic shock, acute kidney injury, severe hypotension, cardiac arrest, and refractory hypotension, but not from myocardial infarction, is provided. The method includes administering a therapeutically effective dose of Angiotensin II, or Ang II, to the patient.
Description
- This patent application is a continuation of U.S. patent application Ser. No. 15/870,139, filed Jan. 12, 2018, which is a continuation of U.S. patent application Ser. No. 15/380,574, filed Dec. 15, 2016 (now U.S. Pat. No. 9,867,863), which is a continuation of U.S. application Ser. No. 12/639,987, filed Dec. 16, 2009 (now U.S. Pat. No. 9,572,856), the entire contents all of which are hereby incorporated by reference.
- The present teachings relate to a therapeutic regimen for patients suffering from at least one of septic shock, acute kidney injury, severe hypotension, cardiac arrest, and refractory hypotension.
- Severe sepsis is the leading cause of acute kidney injury (“AKI”) and its incidence is increasing.
- The two leading clinical conditions associated with AM are sepsis and cardiac surgery. In the largest epidemiologic study to date (>120,000), Bagshaw et al. found that AKI occurred in 36% of intensive care unit patients and that the most common primary diagnosis was sepsis. Similarly, in a large international observational study of AKI requiring renal replacement therapy (RRT), approximately 50% of subjects had sepsis. Direct comparisons of incidence of AKI arising from sepsis vs. cardiac surgery have not been made but two studies in cardiac surgery found incidence rates of 16% and 19% while the incidence in patients with sepsis was twice as great. Furthermore, while the rates of cardiac surgery are steadily declining, sepsis incidence continues to climb. Severe sepsis currently affects more than 750,000 Americans each year and the incidence rises exponentially with age, suggesting that the number of cases will rise in coming years as baby boomers age.
- Patients with septic shock who require high dose vasopressors have a mortality of over 80%. Currently, no specific type of vasopressor (e.g. norepinephrine, vasopressin, dopamine) has been shown to improve outcome. Importantly, patients on high dose catecholamines (e.g., dopamine, epinephrine, norepinephrine) for septic shock often develop tachyphylaxis, limiting the utility of these agents in the sickest patients. Vasopressin, which has been used as an adjuvant with cathecholamines, has not been shown to improve outcomes in patients with septic shock. In the subset of patients whose mean arterial pressure cannot be maintained with current vasopressors, septic shock is uniformly fatal.
- Accordingly, there exists a need for the addition of an effective drug for the treatment of hypotension that does not have the deleterious effects of the present range of treatments.
- The present teachings disclose a method of treating a patient suffering from low blood pressure.
- According to an embodiment of the present teachings, a method of treating a patient suffering from low blood pressure is provided. The patient can suffer from one of septic shock, acute kidney injury, severe hypotension, and refractory hypotension, but not from myocardial infarction. The method can comprise administering a therapeutically effective dose of Angiotensin II (“Ang II”) to the patient.
- The dose of Angiotensin II can be administered at a rate of between about 5 ng/kg/min to about 100 ng/kg/min. The dose of Angiotensin II can be administered at a rate of between about 10 ng/kg/min to about 50 ng/kg/min. The dose of Angiotensin II can be administered at a rate of between about 20 ng/kg/min to about 40 ng/kg/min.
- The dose administration can last from about 0.25 hours to about 120 hours. The dose administration can last from about 1 hour to about 7 hours. The dose administration can last from about 2 hour to about 6 hours. The dose administration can last from about 3 hours to about 5 hours.
- Additional features and advantages of various embodiments will be set forth, in part, in the description that follows, and, in part, will be apparent from the description, or may be learned by practice of various embodiments. The objectives and other advantages of various embodiments will be realized and attained by means of the elements and combinations particularly pointed out in the description herein.
- It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only, and are intended to provide an explanation of various embodiments of the present teachings.
- Ang II is degraded to angiotensin III in a patient, having a half life of a few minutes. Ang II is a direct vasoconstrictor by activating angiotensin I receptors, enhancing peripheral noradrenergic neurotransmission, increasing sympathetic discharge (CNS), and releasing catecholamines from the adrenal medulla.
- Administration of Ang II to patients suffering from at least one of septic shock, acute kidney injury, severe hypotension, cardiac arrest, and refractory hypotension can have adverse side effects, including ischemia, such as, for example, mesenteric ischemia, that damage internal organs. The present teachings disclose a therapeutic regimen of Ang II at doses below that where adverse side effects, such as ischemia, are seen. Furthermore, the therapeutic regimen of Ang II disclosed in the present teachings can act as an adjuvant and lower the effective doses of other therapies, including administration of vasopressin and catecholamine.
- The therapeutic regimen disclosed herein can be started within, for example, 1 hour, 2 hours, 4 hours, 6 hours, or 12 hours after onset of acute symptoms.
- A dose study was designed to determine the feasibility of Ang II as a treatment for sepsis related hypotension.
- A 20 patient randomized blinded study in the treatment of sepsis related hypotension was proposed. Patients suffering from septic shock receiving >15 mcg/min of norepineprhine are eligible. Patients are randomized to Ang II or norepinephrine in a blinded fashion. There are 10 patients in each arm. Norepinephrine is used as a control instead of a true placebo, because the blood pressure rising effects of Ang II would defeat the blinding intent.
- All patients have the treatment of vasopressors titrated to a mean arterial pressure (MAP) of 65 mm of Hg. Patients are then randomized to a control group or arm, or an interventional group or arm treated with Ang II. Patients randomly assigned to the control group are administered with norepinephrine starting at 5 mcg/min, and can be titrated up to 7.5 mcg/mink, and then to 10 mcg/min. Patients in the interventional arm are administered Ang II starting at a dose of about 20 ng/kg/min. Additionally, the dose can then be titrated up to about 30 ng/kg/min. Furthermore, the dose can then be titrated up to about 40 ng/kg/min. The intervention can last for about 4 hours.
- Each patient in the interventional group is started with the assigned starting dose. After the first hour, if the patient is still requiring standing norepinephrine, the dose of the control and interventional drugs can be increased 50%. After the second hour, if the patient is still requiring a standing dose of norepinephrine, the control and interventional drugs can be increased again to twice the initial dose. At the end of 4 hours, the study drug will be titrated off over 30 minutes.
- In the two hours before the initiation of the study drug, all urine is collected. The urine collections are continued for a total duration of nine (9) hours. Blood is drawn at the initiation of the study, four (4) hours thereafter, and then seven (7) hours after. This involves a total of three (3) blood draws of 7 cc of blood per draw for a total of 21 cc of blood. Blood is examined for serum chemistry and serum lactate. In this same time period, demographic and clinical data are collected. Creatinine clearance will be calculated for the pre-study, study, and post-study periods.
- Blood pressure of each patient is monitored continuously from about two (2) hours before initiation of the control and interventional drugs for about seven (7) hours after initiation of the control and interventional drugs.
- Results:
- At the conclusion of the study, 30 day mortality is assessed.
- According to an embodiment of the present teachings, a method of treating a patient suffering from low blood pressure is provided. The patient can suffer from one of septic shock, acute kidney injury, severe hypotension, and refractory hypotension, but not from myocardial infarction. The method can comprise administering a therapeutically effective dose of Angiotensin II (“Ang II”) to the patient.
- The dose of Angiotensin II can be administered at a rate of between about 5 ng/kg/min to about 100 ng/kg/min. The dose of Angiotensin II can be administered at a rate of between about 10 ng/kg/min to about 50 ng/kg/min. The dose of Angiotensin II can be administered at a rate of between about 20 ng/kg/min to about 40 ng/kg/min.
- The dose administration can last from about 0.25 hours to about 120 hours. The dose administration can last from about 1 hour to about 7 hours. The dose administration can last from about 2 hour to about 6 hours. The dose administration can last from about 3 hours to about 5 hours.
- Those skilled in the art can appreciate from the foregoing description that the present teachings can be implemented in a variety of forms. Therefore, while these teachings have been described in connection with particular embodiments and examples thereof, the true scope of the present teachings should not be so limited. Various changes and modifications may be made without departing from the scope of the teachings herein.
- The following publications are herein incorporated by reference in their entireties:
-
- 1. Bagshaw S M, George C, Dinu I, Bellomo R: A Multi-Centre Evaluation of the Rifle Criteria for Early Acute Kidney Injury in Critically Ill Patients. Nephrol Dial Transplant Oct 25 (Epub): 2007
- 2. Uchino S, Kellum J A, Bellomo R, Doig G S, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294:813-818, 2005
- 3. Heringlake M, Knappe M, Vargas H O, et al: Renal dysfunction according to the ADQI-RIFLE system and clinical practice patterns after cardiac surgery in Germany. Minerva Anestesiol 72:645-654, 2006
- 4. Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettila V: Acute renal failure after cardiac surgery: evaluation of the RIFLE classification. Ann Thorac Surg 81:542-546, 2006
- 5. Lopes J A, Jorge S, Resina C, et al: Prognostic utility of RIFLE for acute renal failure in patients with sepsis. Crit Care 11:408, 2007
- 6. Wilson C T, Fisher E S, Welch H G, Siewers A E, Lucas FL: U.S. trends in CABG hospital volume: the effect of adding cardiac surgery programs. Health Aff 26:162-168, 2007
- 7. Angus D C, Linde-Zwirble W T, Lidicker J, Clermont G, Carcillo J, Pinsky M R: Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303-1310, 2001
Claims (31)
1.-29. (canceled)
30. A method of treating severe hypotension in a human subject, comprising administering Angiotensin II to the human subject by intravenous infusion at an initial rate of about 20 ng/kg/min.
31. The method of claim 30 , further comprising titrating the rate up to about 30 ng/kg/min.
32. The method of claim 30 , further comprising titrating the rate up to about 40 ng/kg/min.
33. The method of claim 30 , wherein the rate is titrated up one or more times by about 10 ng/kg/min.
34. The method of claim 30 , wherein the Angiotensin II is administered to the human subject over a period of about 0.25 hours to about 120 hours.
35. The method of claim 34 , wherein the Angiotensin II is administered to the human subject over a period of about 1 hour to about 7 hours.
36. The method of claim 30 , wherein the rate of administration of Angiotensin II is titrated to achieve a mean arterial pressure of about 65 mmHg.
37. The method of claim 30 , wherein the rate of administration of Angiotensin II is titrated to achieve a mean arterial pressure of 65 mmHg.
38. The method of claim 36 , wherein the mean arterial pressure is maintained at about 65 mmHg for about 0.25 hours to about 120 hours.
39. The method of claim 38 , wherein the mean arterial pressure is maintained at about 65 mmHg for about 1 hour to about 7 hours.
40. The method of claim 30 , wherein the subject has septic shock.
41. The method of claim 30 , wherein the severe hypotension is refractory hypotension.
42. The method of claim 30 , wherein the human subject is undergoing treatment with one or more vasopressors.
43. The method of claim 42 , wherein the one or more vasopressors is selected from the group consisting of norepinephrine, vasopressin, epinephrine, and dopamine.
44. The method of claim 43 , wherein the one or more vasopressors is norepinephrine.
45. The method of claim 43 , wherein the one or more vasopressors is vasopressin.
46. The method of claim 42 , further comprising titrating the rate up to about 30 ng/kg/min.
47. The method of claim 42 , further comprising titrating the rate up to about 40 ng/kg/min.
48. The method of claim 42 , wherein the rate is titrated up one or more times by about 10 ng/kg/min.
49. The method of claim 42 , wherein the Angiotensin II is administered to the human subject over a period of about 0.25 hours to about 120 hours.
50. The method of claim 49 , wherein the Angiotensin II is administered to the human subject over a period of about 1 hour to about 7 hours.
51. The method of claim 42 , wherein the rate of administration of Angiotensin II is titrated to achieve a mean arterial pressure of about 65 mmHg.
52. The method of claim 42 , wherein the rate of administration of Angiotensin II is titrated to achieve a mean arterial pressure of 65 mmHg.
53. The method of claim 51 , wherein the mean arterial pressure is maintained at about 65 mmHg for about 0.25 hours to about 120 hours.
54. The method of claim 53 , wherein the mean arterial pressure is maintained at about 65 mmHg for about 1 hour to about 7 hours.
55. A method of treating severe hypotension in a human subject, comprising administering Angiotensin II to the human subject by intravenous infusion at a rate of from about 20 ng/kg/min to about 40 ng/kg/min.
56. The method of claim 55 , wherein the Angiotensin II is administered at a rate of about 30 ng/kg/min.
57. The method of claim 55 , wherein the Angiotensin II is administered at a rate of about 40 ng/kg/min.
58. The method of claim 55 , wherein the subject has septic shock.
59. The method of claim 55 , wherein the severe hypotension is refractory hypotension.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16/725,319 US20200376073A1 (en) | 2009-12-16 | 2019-12-23 | Method of treating low blood pressure |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/639,987 US9572856B2 (en) | 2009-12-16 | 2009-12-16 | Method of treating low blood pressure |
| US15/380,574 US9867863B2 (en) | 2009-12-16 | 2016-12-15 | Method of treating low blood pressure |
| US15/870,139 US10500247B2 (en) | 2009-12-16 | 2018-01-12 | Method of treating low blood pressure |
| US15/922,513 US10322160B2 (en) | 2009-12-16 | 2018-03-15 | Method of treating low blood pressure |
| US16/057,366 US10335451B2 (en) | 2009-12-16 | 2018-08-07 | Method of treating low blood pressure |
| US16/439,881 US10548943B2 (en) | 2009-12-16 | 2019-06-13 | Method of treating low blood pressure |
| US16/725,319 US20200376073A1 (en) | 2009-12-16 | 2019-12-23 | Method of treating low blood pressure |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US16/439,881 Continuation US10548943B2 (en) | 2009-12-16 | 2019-06-13 | Method of treating low blood pressure |
Publications (1)
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| US15/870,139 Active US10500247B2 (en) | 2009-12-16 | 2018-01-12 | Method of treating low blood pressure |
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| US16/439,881 Active US10548943B2 (en) | 2009-12-16 | 2019-06-13 | Method of treating low blood pressure |
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Cited By (3)
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| US11219662B2 (en) | 2016-01-07 | 2022-01-11 | La Jolla Pharma, Llc | Methods for treating hypotension in a patient that has received an ACE inhibitor by administering angiotensin II |
| US11559559B2 (en) | 2013-12-18 | 2023-01-24 | The George Washington University, A Congressionally Chartered Not-For-Profit Corporation | Angiotensin II alone or in combination for the treatment of hypotension |
| US11583568B2 (en) | 2017-04-14 | 2023-02-21 | La Jolla Pharma, Llc | Methods for administering angiotensin II |
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| US9572856B2 (en) | 2009-12-16 | 2017-02-21 | The George Washington University a Congressionally Chartered Not-for-Profit Corporation | Method of treating low blood pressure |
| WO2014087037A1 (en) * | 2012-12-03 | 2014-06-12 | Servicio Andaluz De Salud | Use of the growth factor derived from platelets or a selective agonist of the at2 receptor for the treatment of vascular calcifications |
| WO2014176534A1 (en) | 2013-04-26 | 2014-10-30 | La Jolla Pharmaceutical Company | Compositions and methods for treating renal failure |
| SG11201610897VA (en) * | 2014-07-08 | 2017-01-27 | Jolla Pharma | Methods for treating hypotension |
| US9919022B2 (en) | 2015-03-20 | 2018-03-20 | Arthur J. ATKINSON, JR. | Use of angiotensin II (AII) receptor agonists to prevent or reduce hemodialysis-associated skeletal muscle cramps |
| KR20180108630A (en) * | 2016-01-07 | 2018-10-04 | 라 졸라 파마슈티칼 컴파니 | Method of administration of vasoconstrictor |
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| HU181008B (en) * | 1980-01-18 | 1983-05-30 | Richter Gedeon Vegyeszet | Process for producing angiotenzin-ii analogues of antagonistic activity containing sarcosyl-group at the 1-positon,and an alpha-hydroxy-carboxylic acid at the 8-position |
| US5216025A (en) * | 1989-09-13 | 1993-06-01 | Board Of Regents, The University Of Texas System | Nitric oxide synthesis inhibitors for potentiating the action of pressor agents in certain hypotensive patients |
| US5444067A (en) * | 1993-08-30 | 1995-08-22 | Merck & Co., Inc. | Pharmaceutical treatment methods using angiotensin II receptor agonists bearing a thiophene moiety |
| US6592865B2 (en) * | 2001-06-04 | 2003-07-15 | Human Genome Sciences, Inc. | Methods and compositions for modulating ACE-2 activity |
| US7115266B2 (en) | 2001-10-05 | 2006-10-03 | Cytos Biotechnology Ag | Angiotensin peptide-carrier conjugates and uses thereof |
| US20070293552A1 (en) | 2006-06-15 | 2007-12-20 | Gorczynski Richard J | Antihypertensive therapy method |
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| CN102301235B (en) | 2008-11-28 | 2014-11-19 | Abbvie公司 | Stable Antibody Compositions And Methods For Stabilizing Same |
| US9572856B2 (en) | 2009-12-16 | 2017-02-21 | The George Washington University a Congressionally Chartered Not-for-Profit Corporation | Method of treating low blood pressure |
| EP2593541A4 (en) | 2010-07-14 | 2014-01-22 | Cumberland Emerging Technologies Inc | Methods of treating hepatorenal syndrome and hepatic encephalopathy with thromboxane-a2 receptor antagonists |
| WO2014176534A1 (en) | 2013-04-26 | 2014-10-30 | La Jolla Pharmaceutical Company | Compositions and methods for treating renal failure |
| WO2015095535A1 (en) | 2013-12-18 | 2015-06-25 | The George Washington University, A Congressional Chartered Not-For-Profit Corporation | Angiotensin ii alone or in combination for the treatment of hypotension |
| SG11201610897VA (en) | 2014-07-08 | 2017-01-27 | Jolla Pharma | Methods for treating hypotension |
| KR20180108630A (en) | 2016-01-07 | 2018-10-04 | 라 졸라 파마슈티칼 컴파니 | Method of administration of vasoconstrictor |
| EP3400000B1 (en) | 2016-01-07 | 2023-12-06 | La Jolla Pharma, LLC | Methods for administering angiotensin ii |
| WO2018191678A1 (en) | 2017-04-14 | 2018-10-18 | La Jolla Pharmaceutical Company | Methods for administering angiotensin ii |
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2019
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11559559B2 (en) | 2013-12-18 | 2023-01-24 | The George Washington University, A Congressionally Chartered Not-For-Profit Corporation | Angiotensin II alone or in combination for the treatment of hypotension |
| US11219662B2 (en) | 2016-01-07 | 2022-01-11 | La Jolla Pharma, Llc | Methods for treating hypotension in a patient that has received an ACE inhibitor by administering angiotensin II |
| US11583568B2 (en) | 2017-04-14 | 2023-02-21 | La Jolla Pharma, Llc | Methods for administering angiotensin II |
Also Published As
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| US20190374597A1 (en) | 2019-12-12 |
| US9867863B2 (en) | 2018-01-16 |
| US10322160B2 (en) | 2019-06-18 |
| US9572856B2 (en) | 2017-02-21 |
| US20110144026A1 (en) | 2011-06-16 |
| US20180344800A1 (en) | 2018-12-06 |
| US20180133282A1 (en) | 2018-05-17 |
| US20170095526A1 (en) | 2017-04-06 |
| US10335451B2 (en) | 2019-07-02 |
| US20180200327A1 (en) | 2018-07-19 |
| US10500247B2 (en) | 2019-12-10 |
| US10548943B2 (en) | 2020-02-04 |
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