CA2057834A1 - Pentamidine solution with neutral ph and method for administration thereof - Google Patents
Pentamidine solution with neutral ph and method for administration thereofInfo
- Publication number
- CA2057834A1 CA2057834A1 CA002057834A CA2057834A CA2057834A1 CA 2057834 A1 CA2057834 A1 CA 2057834A1 CA 002057834 A CA002057834 A CA 002057834A CA 2057834 A CA2057834 A CA 2057834A CA 2057834 A1 CA2057834 A1 CA 2057834A1
- Authority
- CA
- Canada
- Prior art keywords
- pentamidine
- solution
- concentration
- pharmaceutically acceptable
- range
- 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.)
- Abandoned
Links
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 title claims abstract description 68
- 229960004448 pentamidine Drugs 0.000 title claims abstract description 65
- 238000000034 method Methods 0.000 title claims abstract description 17
- 230000007935 neutral effect Effects 0.000 title claims description 10
- 239000000243 solution Substances 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 239000003002 pH adjusting agent Substances 0.000 claims description 8
- 229960001624 pentamidine isethionate Drugs 0.000 claims description 8
- YBVNFKZSMZGRAD-UHFFFAOYSA-N pentamidine isethionate Chemical group OCCS(O)(=O)=O.OCCS(O)(=O)=O.C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 YBVNFKZSMZGRAD-UHFFFAOYSA-N 0.000 claims description 8
- 239000001488 sodium phosphate Substances 0.000 claims description 7
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 7
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 7
- 239000004471 Glycine Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 208000000230 African Trypanosomiasis Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 208000005384 Pneumocystis Pneumonia Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 208000029080 human African trypanosomiasis Diseases 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 201000002612 sleeping sickness Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- -1 for example Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT
A small volume aqueous solution of pentamidine or a pharmaceutically acceptable salt thereof having a pH of about 6.5 to about 7.5 and a method for its administration. The concentration of the pentamidine in the solution is in the range of about 0.001 to about 150 mg/ml. The pentamidine solution is administered by mixing either lyophilized pentamidine or a low pH
solution of pentamidine with a solution of sufficient pH
and volume to impart a pH of about 6.5 to about 7.5 to the mixture. The pentamidine concentration in the mixture is about 100 mg/ml. The mixture is then administered to a patient either intravenously, intramuscularly or nebulized and inhaled by the patient.
A small volume aqueous solution of pentamidine or a pharmaceutically acceptable salt thereof having a pH of about 6.5 to about 7.5 and a method for its administration. The concentration of the pentamidine in the solution is in the range of about 0.001 to about 150 mg/ml. The pentamidine solution is administered by mixing either lyophilized pentamidine or a low pH
solution of pentamidine with a solution of sufficient pH
and volume to impart a pH of about 6.5 to about 7.5 to the mixture. The pentamidine concentration in the mixture is about 100 mg/ml. The mixture is then administered to a patient either intravenously, intramuscularly or nebulized and inhaled by the patient.
Description
2 ~ ~ r~ ~ 3 ~
u. .. ~ , . , PENTAMIDINE 50LUTION WITH MEUTRAL pH AND
METHOD FOR ADMINISTRATION THER~OF
Technical Field This invention is directed to a small volume pentamidine solution that has a neutral pH.
Backqround Of The Invention 1,5-Di(4~-amidinophenoxy)pentane, which is generically known as pentamidine, has, for many years, been known for use as a pharmaceutical, in particular for the treatment of the early stages of the African trypanosomiasis ("sleeping sickness") and leishmaniasis.
Pentamidine has also been found to be effective in the treatment of pneumocystis carinii pneumonia ~PCP) a condition which is commonly contracted by patients with acquired immuno~deficiency syndrome (AIDS) and also by cancer and organ transplant patients, and others with severe immuno-deficiencies. It has been estimated that some 6~% of AIDS patients develop PCP.
PCP infection in AIDS patients has been treated by intravenous infusion or intramuscular injection of pentamidine, althouyh this treatment is often accompanied by severe side-effects, e.g.
hypotension, renal failure and hypoglycemia. More recently, there has been reported (Abstracts o~ the Annual Meeting of the American Society of Microbiology 86, 14 (1986)) a method for the prevention of PCP in which a nebulized aqueous solution of pentamidine is administered by inhalation.
Aqueous solutions of pentamidine and pharmaceutically acceptable salts thereof are commonly acidified as disclosed in U.S. Patent No. 4,853,416 to Anaebonam et al. to improve stability and prevent degradation of the pentamidineO Low pH pentamidine solutions can irritate tissue at the site of 2 ~ rJ ~
administration of the drug (e.g. muscle tissue if the drug is administered intramuscularly~.
Alternatively, a pentamidine solu-tion can be stabilized for storage by lyophilization of the pentamidine solution. A solution of pentamidine, or a pharmaceutically acceptable salt thereof, is first frozen and then subjected to a high vacuum 50 that water (ice) vaporizes under vacuum without melting to produce a powder. The lyophilized pentamidine is reconstituted with water prior to administr~tion thereof. The lyophilization process is expensive and requires that the solution and the pentamidine therein be extensively handled Because lyophilization is complex and expensive, it is preferable to store the pentamidine in solution, provided that degradation of the pentamidine can be prevented.
Summary Of The Invention A process is disclosed for the administration of a neutral pH solution of pentamidine or a pharmaceutically acceptable salt thereof. A pentamidine solution of low pH or lyophilized pentamidine is combined with a pH adjusting agent in an amounk sufficient ~o impart a pH o~ about 6.5 to about 7.5 to the resultiny solution. The pH ad~usting agent can be in either liquid or solid form, preferably in liquid fo~m. The resulting neutral pH solution is then administered to the patient. The pentamidine solution is administered intravenously, intramuscularly or by inhalation.
A small volume pentamidine solution with a neutral pH of about 6.5 to about 7.5 is also disclosed herein. The concentration of pentamidine, or a pharmaceutically acceptable salt thereof, is in the range of about 0.001 to about 150 mg/ml of solution, preferably in the range of about 10 to about 130 mg/ml lr~
of solution, more preferably in the range of about 80 to about 110 mg/ml o~ solution, and most preferably about 100 mg/ml of solution.
Detailed Description of The_Preferred Embodiment Pentamidine is unstable in aqueous solutions with a neutral pH. Pentamidine and pharmaceutically acceptable salts thereof (referred to generically herein as pentamidine) degrade in aqueous solutions of neutral pH if stored therein for any length of time.
Pentamidine does not degrade over time when stored in solutions with low pH. Low pH pentamidine solutions can damage tissue when administered.
If the pH of the pentamidine solution is adjusted to neutral immediately prior to administration of the pentamidine, the problems of tissue damage and pentamidine degradation can be avoided. The pH of the pentamidine solution disclosed herein is adjusted to about 6.5 to about 7~5 just prior to the administration of the pentamidine. The pH is adjusted by adding a pH
adjusting agent such as, for example, sodium phosphate, sodium hydroxide, alone or in combination with glycine or potassium hydroxide in either solid or liquid form, to an a~ueous solution o~ pentamidine with a pH of less than about 5Ø Alternatively, lyophilized pentamidine can be reconstituted with a neutralizing solution of the pH adjusting agent and administered to a patienk.
Pharmaceutically acceptable organic salts of pentamidine can also be used in the composition and method of the present invention. Among such salts are gluconate, isethionate, lactate, acetate, tartrate, citrate, phosphate, borate, nitrate and sulfate salts of pentamidine. Pentamidine isethionate is the most preferred salt for this particular application.
2 ~ ~rJ~J~
.,. ;
A chamber containing 300 mg of lyophilized pentamidine isethionate is separated by a seal ~rom another chamber which contains an aqueous sodium phosphate solution with a pH of 8 at a concentration of 0.13 mg/ml sodium phosphate.
The seal between the upper and lower chambers is broken and the sodium phosphate solution is allowed to intermix with the lyophilized pentamidine isethionate. After intermixing, the pentamidine salt solution, with a pH of 7, can be withdrawn by a syringe and administered either intravenously or intramuscularly, or nebulized and administered by inhalation.
A chamber containing 300 mg of lyophilized pentamidine isethionate is separated by a seal from another chamber which contains an aqueous glycine/sodium hydroxide solution with a pH of 7.5 at a concentration ~o of 7.5 mg/ml.
The seal between the upper and lower chambers is broken and the glycine/sodium hydroxide solution is allowed to intermix with the lyophilized pentamidine isethionate. After intermixin~, the pentamidine salt solution, with a pH of 7.2, can be wi-thdrawn by a syringe and administered either intravenously or intramuscularly, or nebulized and administered by inhalation.
The foregoing discussion and examples are
u. .. ~ , . , PENTAMIDINE 50LUTION WITH MEUTRAL pH AND
METHOD FOR ADMINISTRATION THER~OF
Technical Field This invention is directed to a small volume pentamidine solution that has a neutral pH.
Backqround Of The Invention 1,5-Di(4~-amidinophenoxy)pentane, which is generically known as pentamidine, has, for many years, been known for use as a pharmaceutical, in particular for the treatment of the early stages of the African trypanosomiasis ("sleeping sickness") and leishmaniasis.
Pentamidine has also been found to be effective in the treatment of pneumocystis carinii pneumonia ~PCP) a condition which is commonly contracted by patients with acquired immuno~deficiency syndrome (AIDS) and also by cancer and organ transplant patients, and others with severe immuno-deficiencies. It has been estimated that some 6~% of AIDS patients develop PCP.
PCP infection in AIDS patients has been treated by intravenous infusion or intramuscular injection of pentamidine, althouyh this treatment is often accompanied by severe side-effects, e.g.
hypotension, renal failure and hypoglycemia. More recently, there has been reported (Abstracts o~ the Annual Meeting of the American Society of Microbiology 86, 14 (1986)) a method for the prevention of PCP in which a nebulized aqueous solution of pentamidine is administered by inhalation.
Aqueous solutions of pentamidine and pharmaceutically acceptable salts thereof are commonly acidified as disclosed in U.S. Patent No. 4,853,416 to Anaebonam et al. to improve stability and prevent degradation of the pentamidineO Low pH pentamidine solutions can irritate tissue at the site of 2 ~ rJ ~
administration of the drug (e.g. muscle tissue if the drug is administered intramuscularly~.
Alternatively, a pentamidine solu-tion can be stabilized for storage by lyophilization of the pentamidine solution. A solution of pentamidine, or a pharmaceutically acceptable salt thereof, is first frozen and then subjected to a high vacuum 50 that water (ice) vaporizes under vacuum without melting to produce a powder. The lyophilized pentamidine is reconstituted with water prior to administr~tion thereof. The lyophilization process is expensive and requires that the solution and the pentamidine therein be extensively handled Because lyophilization is complex and expensive, it is preferable to store the pentamidine in solution, provided that degradation of the pentamidine can be prevented.
Summary Of The Invention A process is disclosed for the administration of a neutral pH solution of pentamidine or a pharmaceutically acceptable salt thereof. A pentamidine solution of low pH or lyophilized pentamidine is combined with a pH adjusting agent in an amounk sufficient ~o impart a pH o~ about 6.5 to about 7.5 to the resultiny solution. The pH ad~usting agent can be in either liquid or solid form, preferably in liquid fo~m. The resulting neutral pH solution is then administered to the patient. The pentamidine solution is administered intravenously, intramuscularly or by inhalation.
A small volume pentamidine solution with a neutral pH of about 6.5 to about 7.5 is also disclosed herein. The concentration of pentamidine, or a pharmaceutically acceptable salt thereof, is in the range of about 0.001 to about 150 mg/ml of solution, preferably in the range of about 10 to about 130 mg/ml lr~
of solution, more preferably in the range of about 80 to about 110 mg/ml o~ solution, and most preferably about 100 mg/ml of solution.
Detailed Description of The_Preferred Embodiment Pentamidine is unstable in aqueous solutions with a neutral pH. Pentamidine and pharmaceutically acceptable salts thereof (referred to generically herein as pentamidine) degrade in aqueous solutions of neutral pH if stored therein for any length of time.
Pentamidine does not degrade over time when stored in solutions with low pH. Low pH pentamidine solutions can damage tissue when administered.
If the pH of the pentamidine solution is adjusted to neutral immediately prior to administration of the pentamidine, the problems of tissue damage and pentamidine degradation can be avoided. The pH of the pentamidine solution disclosed herein is adjusted to about 6.5 to about 7~5 just prior to the administration of the pentamidine. The pH is adjusted by adding a pH
adjusting agent such as, for example, sodium phosphate, sodium hydroxide, alone or in combination with glycine or potassium hydroxide in either solid or liquid form, to an a~ueous solution o~ pentamidine with a pH of less than about 5Ø Alternatively, lyophilized pentamidine can be reconstituted with a neutralizing solution of the pH adjusting agent and administered to a patienk.
Pharmaceutically acceptable organic salts of pentamidine can also be used in the composition and method of the present invention. Among such salts are gluconate, isethionate, lactate, acetate, tartrate, citrate, phosphate, borate, nitrate and sulfate salts of pentamidine. Pentamidine isethionate is the most preferred salt for this particular application.
2 ~ ~rJ~J~
.,. ;
A chamber containing 300 mg of lyophilized pentamidine isethionate is separated by a seal ~rom another chamber which contains an aqueous sodium phosphate solution with a pH of 8 at a concentration of 0.13 mg/ml sodium phosphate.
The seal between the upper and lower chambers is broken and the sodium phosphate solution is allowed to intermix with the lyophilized pentamidine isethionate. After intermixing, the pentamidine salt solution, with a pH of 7, can be withdrawn by a syringe and administered either intravenously or intramuscularly, or nebulized and administered by inhalation.
A chamber containing 300 mg of lyophilized pentamidine isethionate is separated by a seal from another chamber which contains an aqueous glycine/sodium hydroxide solution with a pH of 7.5 at a concentration ~o of 7.5 mg/ml.
The seal between the upper and lower chambers is broken and the glycine/sodium hydroxide solution is allowed to intermix with the lyophilized pentamidine isethionate. After intermixin~, the pentamidine salt solution, with a pH of 7.2, can be wi-thdrawn by a syringe and administered either intravenously or intramuscularly, or nebulized and administered by inhalation.
The foregoing discussion and examples are
3~ intended to illustrate the general concepts disclosed herein and defined by the claims appended hereto. The discussion and examples are not intended to limit the invention disclosed herein in any manner.
Claims (18)
1. A small volume pharmaceutical composition comprising an aqueous solution of pentamidine or a pharmaceutically acceptable salt thereof, the solution having a concentration of pentamidine or a pharmaceutically acceptable salt thereof in the range of about 0.001 to about 150 mg/ml and a pH of about 6.5 to about 7.5.
2. The composition of claim 1 wherein the pentamidine concentration is in the range of about 10 to about 130 mg/ml of solution.
3. The composition of claim 1 wherein the pentamidine concentration is in the range of about 80 to about 110 mg/ml of solution.
4. The composition of claim 1 wherein the pentamidine concentration is about 100 mg/ml of solution.
5. The composition of claim 1 wherein the pharmaceutically acceptable pentamidine salt is pentamidine isethionate.
6. The composition of claim 1 wherein a pH
adjusting agent is present in an amount sufficient to impart the desired pH to the aqueous pentamidine solution.
adjusting agent is present in an amount sufficient to impart the desired pH to the aqueous pentamidine solution.
7. The composition of claim 6 wherein the pH
adjusting agent is selected from the group consisting of sodium phosphate, potassium hydroxide, sodium hydroxide and a mixture of sodium hydroxide and glycine.
adjusting agent is selected from the group consisting of sodium phosphate, potassium hydroxide, sodium hydroxide and a mixture of sodium hydroxide and glycine.
g. A method for the administration of an aqueous solution of pentamidine comprising:
adding a sufficient amount of a pH
adjusting agent to an aqueous solution comprising pentamidine or a pharmaceutically acceptable salt thereof with a pH of less than 5.0 to impart a neutral pH of about 6.5 to about 7.5 to the pentamidine solution; and administering the combined pentamidine solution to a patient.
adding a sufficient amount of a pH
adjusting agent to an aqueous solution comprising pentamidine or a pharmaceutically acceptable salt thereof with a pH of less than 5.0 to impart a neutral pH of about 6.5 to about 7.5 to the pentamidine solution; and administering the combined pentamidine solution to a patient.
9. The method of claim 8 wherein the concentration of pentamidine in the neutral pH
pentamidine solution is in the range of 0.001 to about 150 mg/ml.
pentamidine solution is in the range of 0.001 to about 150 mg/ml.
10. The method of claim g wherein the pentamidine concentration is in the range of about 10 to about 130 mg/ml of solution.
11. The method of claim 9 wherein the pentamidine concentration is in the range of about 80 to about 110 mg/ml of solution.
12. The method of claim 9 wherein the pentamidine concentration is about 100 mg/ml of solution.
13. The method of claim 5 wherein the pharmaceutically acceptable salt of pentamidine is pentamidine isethionate.
14. The method of claim 9 wherein the pH
adjusting agent is selected from the group consisting of sodium phosphate, potassium hydroxide, sodium hydroxide and a mixture of sodium hydroxide and glycine.
adjusting agent is selected from the group consisting of sodium phosphate, potassium hydroxide, sodium hydroxide and a mixture of sodium hydroxide and glycine.
15. A method for the administration of an aqueous solution of pentamidine comprising:
reconstituting a lyophilized pentamidine or lyophilized pharmaceutically acceptable salt of pentamidine with an aqueous pH adjusting solution in an amount sufficient to impart a pH of about 6.5 to about 7.5 to the resulting reconstituted pentamidine solution;
and administering the reconstituted pentamidine solution to a patient.
reconstituting a lyophilized pentamidine or lyophilized pharmaceutically acceptable salt of pentamidine with an aqueous pH adjusting solution in an amount sufficient to impart a pH of about 6.5 to about 7.5 to the resulting reconstituted pentamidine solution;
and administering the reconstituted pentamidine solution to a patient.
16. The method of claim 15 wherein the concentration of lyophilized pentamidine in the reconstituted solution is in the range of about 0.001 to about 150 mg/ml.
17. The method of claim 15 wherein the pharmaceutically acceptable salt of pentamidine is pentamidine isethionate.
18. The method of claim 15 wherein the pH
adjusting agent is selected from the group consisting of sodium phosphate, potassium hydroxide, sodium hydroxide and a mixture of sodium hydroxide and glycine.
adjusting agent is selected from the group consisting of sodium phosphate, potassium hydroxide, sodium hydroxide and a mixture of sodium hydroxide and glycine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63425990A | 1990-12-26 | 1990-12-26 | |
| US634,259 | 1990-12-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2057834A1 true CA2057834A1 (en) | 1992-06-27 |
Family
ID=24543049
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002057834A Abandoned CA2057834A1 (en) | 1990-12-26 | 1991-12-17 | Pentamidine solution with neutral ph and method for administration thereof |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2057834A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002036588A3 (en) * | 2000-11-06 | 2003-08-28 | Us Army Med Res Mat Command | Reversed amidines and methods of using for treating, preventing, or inhibiting leishmaniasis |
-
1991
- 1991-12-17 CA CA002057834A patent/CA2057834A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002036588A3 (en) * | 2000-11-06 | 2003-08-28 | Us Army Med Res Mat Command | Reversed amidines and methods of using for treating, preventing, or inhibiting leishmaniasis |
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| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |