Hostname: page-component-7857688df4-7g6pc Total loading time: 0 Render date: 2025-11-15T15:31:12.073Z Has data issue: false hasContentIssue false
  • English
  • Français

Pentamidine: A Review

Published online by Cambridge University Press:  21 March 2023

Brian Wispelwey  and
Richard D. Pearson
Brian Wispelwey*
Affiliation:
Departments of Internal Medicine and Pathology, the Divisions of Infectious Diseases and Geographic Medicine, the University of Virginia, Charlottesville, Virginia
Richard D. Pearson
Affiliation:
Departments of Internal Medicine and Pathology, the Divisions of Infectious Diseases and Geographic Medicine, the University of Virginia, Charlottesville, Virginia
*
University of Virginia, Division of Infectious Diseases, Box 397, Charlottesville, VA 22908
Get access Rights & Permissions [Opens in a new window]

Extract

With the advent of the acquired immunodeficiency syndrome (AIDS), the therapeutic importance of pentamidine isethionate has increased greatly. This review summarizes the pharmacology, clinical experience in the treatment of Pneumocystis carinii pneumonia, and toxicity of pentamidine. Data are conflicting as to whether pentamidine is more or less effective than trimethoprim-sulfamethoxazole (TMP-SX) for the treatment of P carinii pneumonia in individuals with AIDS, but due to its toxicity and expense, it is considered as second-line therapy for P carinii pneumonia by many authorities. Hypoglycemia has been encountered in up to 27%, and nephrotoxicity in 25%, of treatment courses with pentamidine. In an attempt to circumvent the toxicities associated with parenteral administration, aerosolized delivery has been evaluated for both therapy and prevention of P carinii pneumonia. Aerosolized pentamidine, on the basis of early clinical results, convenience, and low toxicity, is being used extensively to prevent P carinii pneumonia in individuals at high risk. Relapses occur, however, and pneumothorax may be more common in those using this form of prophylaxis. Aerosolized pentamidine should not be used as sole therapy for acute P carinii pneumonia.

Information

Type
Clinical Pharmacology of Antibiotics
Information
Infection Control & Hospital Epidemiology , Volume 12 , Issue 6 , June 1991 , pp. 375 - 382
Copyright
Copyright © The Society for Healthcare Epidemiology of America 1991 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1. King, H, Lourie, EM, York, W. Studies in chemotherapy XIX: further report on new trypanocidal substances. Ann Trop Med Parasitol. 1938;32:177–192.Google Scholar
2. Ivady, G, Paldy, L. Treatment of Pneumocystis carinii pneumonia in infancy. National Cancer Institute Monographs. 1976;43:201–209.Google Scholar
3. Waalkes, TP, Denham, C, De Vita, VT Pentamidine: clinical pharmacologic correlations in man and mice. Clin Pharmacol Ther. 1970;11:505–512.Google Scholar
4. Conte, JE, Upton, RA, Lin, ET. Pentamidine pharmacokinetics in patients with AIDS with impaired renal function. J Infect Dis. 1987;156:885–890.Google Scholar
5. Sands, M, Kron, MA, Brown, RB. Pentamidine: a review . Rev Infect Dis. 1985;7:625–634.Google Scholar
6. Fitzsimmons, WE, Luskin, SS. Pentamidine therapy in renal failure: case report and literature review. Drug Intell Clin Pharm. 1988;22:25–28.Google Scholar
7. Vohringer, HF, Arasteh, K, Hardtmann, E. Distribution of pentamidine after intravenous and inhaled application in AIDS patients. 6th International Conference on AIDS; June 20-24, 1990; San Francisco, Calif: Abstract Th. B. 416.Google Scholar
8. Donnelly, H, Bernard, EM, Rothkotter, H, et al. Distribution of pentamidine in patients with AIDS. J Infect Dis. 1988;157:985–989.Google Scholar
9. Wingen, F, Bragas, B. Autoradiographic examination of the organ distribution of 14C-labelled nentamidine in rats after IV and inhalative administration. 6th international Conference on AIDS; June 20-24, 1990; San Francisco, Calif: Abstract Th. B. 418.Google Scholar
10. Conte, JE, Chemoff, D, Feigal, DW, Joseph, P, McDonald, C, Golden, JA. Intravenous and inhaled nentamidine for treating Pneumocystis carinii pneumonia in AIDS. Ann Intern Med. 1990;113:203–209.Google Scholar
11. Navin, TR, Diekinson, CM, Adams, SR, et al. Effect of azotemia in dogs on the pharmacokinetics of pentamidine. J Infect Dis. 1987;155:1020–1026.Google Scholar
12. Sattler, FR, Cowan, R, Niielsen, DM, Ruskin, J. Trimethoprim-sulfamethoxazole compared with pentamidine for the treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med. 1988;109:280–287.Google Scholar
13. Debs, RJ, Straubinger, RM, Brunette, EN, et al. Selective enhancement of pentamidine uptake in the lung by aerosolization and delivery in liposomes. Am Rev Resp Dis. 1987;135:731–737.Google Scholar
14. Monteomery, AB. Debs, RI. Luce, TM. et al. Selective delivery of pentamidine to the lung by aerosol. Am Rev Resp Dis. 1988;137:477–478.Google Scholar
15. Conte, JE, Golden, JA. Concentrations of aerosolized pentamidine in bronchoalveolar lavage, systemic absorptions, and excretion. Antimicrob Agents Chemother. 1988;32:1490–1493.Google Scholar
16. Williamson, J. Effects of trypanocides on the tine structure of target oreanisms. Pharmacol Ther. 1979;7:445–512.Google Scholar
17. Pearson, RD, Hewlett, EL. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal disease. Ann Intern Med. 1985;103:782–786.Google Scholar
18. Ivady, G, Paldy, L, Koltay, M, et al. Pneumocystis carinii pneumonia. Lancet. 1967;i:616–617.Google Scholar
19. Walzer, PD, Perl, DP, Krogstad, DJ, et al. Pneumocystis cariniii pneumonia in the United States. Ann Intern Med. 1974;80:83–93.Google Scholar
20. Hughes, WT, Feldman, S, Chaudhary, SC, et al. Comparison of pentamidine isethionate and trimethoprim-sulfmethoxazole in the treatment of Pneumocystis carinii pneumonia. J pediatr. 1978;92:285–291.Google Scholar
21. Hughes, WT, Feldman, S, Sanyalsk, . Treatment of Pneumoqstis carinii pneumonia with trimethoprim-sulfamethoxazole. Can Med Assoc J. 1975;112(suppl):47–50.Google Scholar
22. Mallory, DL, Parillo, JE, Bailey, KR, et al. Cardiovascular effects and safety of intravenous and intramuscular pentamidine isethionate. Crit Care Med. 1987;15:503–505.Google Scholar
23. Navin, TR, Fontaine, RE. Intravenous versus intramuscular administration of pentamidine. N Engl J Med. 1984;311:1701–1702.Google Scholar
24. Small, CB. Harris, CA. Friedland, GH. Klein, RS. The treatment of Pneumocystis carinii' pneumonia in' the acquired immunodeficiency syndrome. Arch Intern Med. 1985;145:837–840.Google Scholar
25. Wharton, TM. Coleman, DL. Wofsy, CB. et al. Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med. 1986;105:37–44.Google Scholar
26. Conte, JE, Hollander, H, Golden, JA. Inhaled or reduced dose intravenous pentamidine for Pneumocystis curinii pneumonia: a pilot study. Ann Intern Med. 1987;107:495–498.Google Scholar
27. Montgomery, AB, Luce, JM, Turner, J, et al. Aerosolized pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Lancet. 1987;ii:480–483.Google Scholar
28. Montgomery, AB, Debs, RJ, Luce, JM, et al. Aerosolized pentamidine as second-line therapy in patients with AIDS and Pneumocystis carinii pneumonia. Chest. 1989;95:747–750.Google Scholar
29. Soo Hoo, GW, Mohsenifar, Z, Meyer, RD. Inhaled or intravenous pentamidine therapy for Pneumocystis carinii pneumonia. Ann Intern Med. 1990;113:195–202.Google Scholar
30. Montgomery, AB, Edison, RE, Sattler, F, et al. Aerosolized pentamidine vs. trimethoprim/sulfamethoxazole for acute Pneumocystis carinii pneumonia. 6th International Conference on AIDS; June 20-24, 1990; San Francisco, Calif: Abstract Th. B. 395.Google Scholar
31. O'Doherty, MJ, Page, C, Bradbeer, C, et al. Differences in relative efficiency of nebulizers for pentamidine administration. Lancet. 1988;ii:1283–1286.Google Scholar
32. Leoung, GS, Feigal, DW, Montgomery, AB et al. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. N Engl J Med. 1990;323:769–775.Google Scholar
33. Masur, H, Ognibene, FP, Yarchoan, R, et al. CD, counts as predictors of opportunistic pneumonias in human immunodeficiency virus infection. Ann Intern Med. 1989;114:223–231.Google Scholar
34. Raviglione, MC, Currier, JS. Low-dose TMP-SX for PCP prophy1axis. AIDS Clinical Cure. 1991;3:21–22.Google Scholar
35. Golden, JA. Hollander, H. Chemoff, D. et al. Prevention of Pneumocystis carinii pneumonia by inhaled pentamidine. Luncet. 1989;i:654–657.Google Scholar
36. Girard, P-M, Gaudebout, C, Lottin, P, et al. Prevention of Pneumocystis carinii pneumonia relapse by pentamidine aerosol in zidovadine-treated AIDS patients. Lancet. 1989;i:1348–1353.Google Scholar
37. Abd, AG, Weitman, DM, Ilowite, JS, et al. Bilateral upper lobe Pneumocystis carinii pneumonia in a patient receiving inhaled pentamidine prophylaxis. Chest. 1988;94:329–331.Google Scholar
38. Jules-Elysee, KM, Stover, DE, Zaman, MB, Bernard, EM, White, DA. Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. Ann Intern Med. 1990;112:750–757.Google Scholar
39. Baskin, MI, Abd, AG, Ilowite, JS. Regional deposition of pentamidine. Ann Intern Med. 1990;113:677–683.Google Scholar
40. Sepkowitz, KA, Telzak, FE, Gold, JWM, et al. Pneumothorax in AIDS. Ann Intern Med. 1991;114:455–459.Google Scholar
41. Raviglione, MC. Extrapulmonary pneumocystosis: the first 50 cases. Rev Infect Dis. 1990;12:1125–1138.Google Scholar
42. Western, KA, Perera, DR, Schultz, MG. Pentamidine isethionate in the treatment of Pneumocystis carinii pneumonia. Ann Intern Med. 1970;73:695–702.Google Scholar
43. Murphy, SA, Josephs, AS. Acute pancreatitis associated with pentamidine therapy. Arch Intern Med. 1981;141:56–58.Google Scholar
44. Salmeron, S, Petitpretz, P, Katlama, , et al. Pentamidine and pancreatitis. Ann Intern Med. 1986;105:140–141.Google Scholar
45. Zuger, A, Wolf, BZ, El Sadr, W, et al. Pentamidine-associated fatal acute pancreatitis. JAMA. 1986;256:2383–2385.Google Scholar
46. Kumar, S, Schadig, VJ, MacGregor, MG. Fatal acute pancreatitis associated with pentamidine therapy. Am J Gastroenterol. 1989;84:451–453.Google Scholar
47. Stahl-Bayliss, CM, Kalman, CM, Laskin, OL. Pentamidine-induced hypoglycemia in patients with the acquired immune deficiency syndrome. Clin Pharmacol Ther. 1986;39:271–175.Google Scholar
48. Bouchard, PH, Sai, P, Reach, G, et al. Diabetes mellitus following pentamidine-induced hypoglycemia in humans. Diabetes. 1982;31:40–45.Google Scholar
49. Rerup, CC. Drugs producing diabetes through damage of insulinsecreting cells. Pharmacol Rev. 1970;22:485–518.Google Scholar
50. Sai, P, Boillot, D, Boitard, C, et al. Pentamidine, a new diabetogenie drug in laboratory rodents. Diabetologia. 1983;25:418–423.Google Scholar
51. Fitzgerald, DB, Young, IS. Reversal of pentamidine-induced hypoglycemia with oral diazoxide. J Trop Med Hyg. 1984;87:15–19.Google Scholar
52. Collins, RJ, Pien, FD, Houk, JH. Case report: insulin-dependent diabetes mellitus associated with pentamidine. Am J Med Sci. 1989;297:174–175.Google Scholar
53. Waskin, H, Hardy, WD, McClain, N, Fall, H. Diabetes mellitus in HIV-positive patients post-pneumocystis pneumonia and the impact of aerosolized pentamidine. 6th International Conference on AIDS, June 20-24, 1990; San Francisco, Calif: Abstract Th. B. 422.Google Scholar
54. Zhou, DB, Ipp, E. Pentamidine-induced p-cell toxicity is not preventable by high glucose. Am J Med Sci. 1989;298:89–92.Google Scholar
55. Lachaal, M, Venuto, RC. Nephrotoxicity and hyperkalcemia in patients with acquired immunodeficiency syndrome treated with pentamidine. Am J Med. 1989;87:260–263.Google Scholar
56. Wharton, JM, Demopulos, PA, Goldschlager, N. Torsade de pointes during administration of pentamidine isethionate. Am J Med. 1987;83:571–575.Google Scholar
57. Bibler, MR, Chou, T-C, Toltzis, RJ, Wade, PA. Recurrent ventricular tachycardia due to pentamidine-induced cardiotoxicity. Chest. 1988;94:1306.Google Scholar
58. Smith, DE, Herd, D, Guzzard, BG. Reversible bronchoconstriction with nebulized pentamidine. Lancet. 1988;ii:905.Google Scholar
59. Herer, B, Chinet, T, Labrune, S, et al. Pancreatitis associated with pentamidine by aerosol. B Med J. 1989;298:605.Google Scholar
60. Karboski, JA, Godley, PJ. Inhaled pentamidine and hypoglycemia. Ann Intern Med. 1988;108:490.Google Scholar
61. Berger, TG, Tapper-o, JW, Leoung, GS, Jacobsen, MA. Aerosolized pentamidine and cutaneous eruptions. Ann Intern Med. 1989;110:1035–1036.Google Scholar
62. Montgomery, AB, Corker-y, KJ, Brunette, ER, Leoung, GS, Waskin, H, Debs, RJ. Occupational exposure to aerosolized pentamidine. Chest. 1990;98:386–388.Google Scholar
63. Centers for Disease Control. Mycobacterium tuberculosis transmission in a health clinic. Florida, 1988. MMWR. 1989;38:256–258.Google Scholar