Suppression of Pneumocystis carinii using aerosolized pentamidine treatment

• US 5,366,726 A
• Filed: 07/23/1992
• Issued: 11/22/1994
• Est. Priority Date: 12/23/1987
• Status: Expired due to Fees

• Current Assignee: Jeffrey A. Golden, John E. Conte Jr, Montgomery A. Bruce, Robert C. Debs
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Montgomery, Alan B., Golden, Jeffrey A., Conte, John E., Debs, Robert J.
• Primary Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US07/918,884
• Time in Patent Office: 852 Days
• Field of Search: 424/45, 424/88, 239/338, 514/809, 514/357, 514/394, 514/631, 514/637
• US Class Current: 424/45
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61M 11/06 of the injector type
• CPC Class Codes: A61M 16/08 Bellows; Connecting tubes having means for taking samples G01N1/22; Water traps; Patient circuits
• CPC Class Codes: A61M 16/1065 in the expiratory path

Abstract

A method of preventing clinically manifest Pneumocystis carinii pneumonia in immunocompromised humans is provided wherein an aerosol of pentamidine is administered to the patient in a manner which delivers the aerosol to the patient'"'"'s alveoli. Also provided is a method of treating Pneumocystis carinii pneumonia in HIV seropositive individuals comprising administering a therapeutically effective amount of pentamidine aerosol to the HIV positive individual through inhalation. In addition, a method is provided of administering pentamidine to a human comprising aerosolizing a pentamidine solution in a nebulizer system having a one-way valve disposed between the nebulizer and the mouthpiece of the nebulizer system.

Claims

1. A method of treating Pneumonia caused by Pneumocystis carinii in a human patient by providing a pentamidine aerosol having a mean particle diameter from about 0.25 to about 5 μ

m and administering an Pharmaceutically effective amount of said aerosol to a patient suffering from Pneumocystis carinii pulmonary infection, whereby said aerosol is delivered to said patient'"'"'s alveoli using a nebulizer consisting essentially of;

(a) a tube providing an oxygen flow into the nebulizer;

(b) a nebulizer container holding the pentamidine solution for generation of aerosolized particles in a conduit;

(c) the conduit;

(d) a mouthpiece;

(e) a one way valve having a baffle for reducing larger particle sizes to particles having a mean diameter from about 0.25 to about 5 μ

m; and

(f) a one way valve leading to particle filter for removal of residual pentamidine during exhalation.

2. The method of claim 1 wherein the mean particle diameter of said aerosol is from about 0.5 to about 2.5 μ

m.

3. The method of claim 2 wherein the mean particle diameter of said aerosol is from about 1 to about 2 μ

m.

4. The method of claim 1 wherein said patient is an immunocompromised individual suffering from AIDS, ARC, or an individual treated with immunosuppressive drugs.

5. The method of claim 1 wherein said patient is HIV seropositive.

6. The method of claim 4 wherein said patient is immunocompromised due to chemotherapy or radiotherapy.

7. The method of claim 6 wherein said pentamidine aerosol is administered at least every third day for about 4 to about 30 days.

8. The method of claim 7 wherein said pentamidine aerosol is administered at least every second day for about 4 to about 21 days.

9. The method of claim 8 wherein said pentamidine aerosol is administered about every day for about 4 to about 21 days.

10. The method of claim 6 wherein said effective amount comprises about 30 mg per one pentamidine aerosol treatment.

11. The method of claim 6 wherein said effective amount comprises about 100 mg per one pentamidine aerosol treatment.

12. The method of claim 6 wherein said effective amount comprises about 300 mg per one pentamidine aerosol treatment.

13. The method of claim 6 wherein said effective amount comprises about 600 mg per one pentamidine aerosol treatment.

15. The method of claim 1, wherein said Pneumonia is clinically manifest and wherein said amount of an aerosol suspension of pentamidine sufficient to treat said infection is about 160 mg to about 600 mg and is delivered via said nebulizer to said patient at least every second day for about 4 to about 30 days.

16. The method of claim 1, wherein said Pneumonia is clinically manifest and wherein said amount of an aerosol suspension of pentamidine sufficient to treat said infection is about 160 mg to about 600 mg and is delivered via said nebulizer to said patient at least every second day for about 4 to about 21 days.

17. The method of claim 1, wherein said Pneumonia is clinically manifest and wherein said amount of an aerosol suspension of pentamidine sufficient to treat said Pneumonia is about 160 mg to about 600 mg and is delivered via said nebulizer to said patient at least about daily for about 4 to about 21 days.

14. A method for inhibiting the growth of Pneumocystis carinii in a human being by delivering, by inhalation, to the respiratory system of a patient suffering from Pneumonia causing Pneumocystis carinii, an aerosol suspension of pentamidine, having a mean particle diameter within a range from about 0.25 μ

m to about 2.5 μ

m using a nebulizer consisting essentially of;

(a) a tube providing an oxygen flow into the nebulizer;

(b) a nebulizer container holding a pentamidine solution for generation of aerosolized particles in a conduit;

(c) the conduit;

(d) a mouthpiece;

(e) a one way valve having a baffle for reducing larger particle sizes to particles having a mean diameter from about 0.25 to about 5 μ

m; and

(f) a one way valve leading to particle filter for removal of residual pentamidine during exhalation;

wherein said pentamidine suspension is delivered in an amount sufficient to inhibit the growth of Pneymocystis carinii.