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. 1997 May;41(5):1077–1081. doi: 10.1128/aac.41.5.1077

Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients.

M Cruciani 1, G Gatti 1, C Mengoli 1, A Cazzadori 1, L Lazzarini 1, F Miletich 1, M S Graziani 1, M Malena 1, D Bassetti 1
PMCID: PMC163854  PMID: 9145873

Abstract

We studied the penetration of dapsone into the epithelial lining fluid (ELF) of sixteen human immunodeficiency virus type 1-infected patients who had received the drug at a dose of 100 mg twice weekly as primary prophylaxis for Pneumocystis carinii pneumonia. Bronchoscopy, bronchoalveolar lavage (BAL), and venipuncture were performed for each patient at a specific time after administration of the last dose of dapsone. Dapsone concentrations in plasma and BAL were determined by high-performance liquid chromatography. The apparent volume of ELF recovered by BAL was determined by using urea as an endogenous marker. The mean concentrations of dapsone in ELF at 2 h (five patients), 4 h (three patients), 12 h (two patients), 24 h (three patients), and 48 h (three patients) were 0.95, 0.70, 1.55, 0.23, and 0.45 mg/liter, respectively, while concentrations in plasma were 1.23, 0.79, 1.31, 0.83, and 0.18 mg/liter, respectively. Dapsone concentrations in ELF were 76, 79, 115, 65, and 291% of those observed in plasma at the same times, respectively. These data show that dapsone is well distributed into ELF and that a twice-weekly 100-mg prophylactic regimen results in sustained concentrations in this compartment.

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Selected References

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  1. Antinori A., Murri R., Ammassari A., De Luca A., Linzalone A., Cingolani A., Damiano F., Maiuro G., Vecchiet J., Scoppettuolo G. Aerosolized pentamidine, cotrimoxazole and dapsone-pyrimethamine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis. AIDS. 1995 Dec;9(12):1343–1350. doi: 10.1097/00002030-199512000-00007. [DOI] [PubMed] [Google Scholar]
  2. Baldwin D. R., Honeybourne D., Wise R. Pulmonary disposition of antimicrobial agents: in vivo observations and clinical relevance. Antimicrob Agents Chemother. 1992 Jun;36(6):1176–1180. doi: 10.1128/aac.36.6.1176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blum R. N., Miller L. A., Gaggini L. C., Cohn D. L. Comparative trial of dapsone versus trimethoprim/sulfamethoxazole for primary prophylaxis of Pneumocystis carinii pneumonia. J Acquir Immune Defic Syndr. 1992;5(4):341–347. [PubMed] [Google Scholar]
  4. Bozzette S. A., Finkelstein D. M., Spector S. A., Frame P., Powderly W. G., He W., Phillips L., Craven D., van der Horst C., Feinberg J. A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995 Mar 16;332(11):693–699. doi: 10.1056/NEJM199503163321101. [DOI] [PubMed] [Google Scholar]
  5. Cruciani M., Bertazzoni Minelli E., Mirandola M., Luzzati R., Merighi M., Lazzarini L., Gatti G., Vento S., Mazzi R., Malena M. Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data. Clin Microbiol Infect. 1996 Aug;2(1):30–35. doi: 10.1111/j.1469-0691.1996.tb00197.x. [DOI] [PubMed] [Google Scholar]
  6. Cushion M. T., Stanforth D., Linke M. J., Walzer P. D. Method of testing the susceptibility of Pneumocystis carinii to antimicrobial agents in vitro. Antimicrob Agents Chemother. 1985 Dec;28(6):796–801. doi: 10.1128/aac.28.6.796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Falloon J., Lavelle J., Ogata-Arakaki D., Byrne A., Graziani A., Morgan A., Amantea M. A., Ownby K., Polis M., Davey R. T., Jr Pharmacokinetics and safety of weekly dapsone and dapsone plus pyrimethamine for prevention of pneumocystis pneumonia. Antimicrob Agents Chemother. 1994 Jul;38(7):1580–1587. doi: 10.1128/aac.38.7.1580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gatti G., Loy A., Casazza R., Miletich F., Cruciani M., Bassetti D. Pharmacokinetics of dapsone in human immunodeficiency virus-infected children. Antimicrob Agents Chemother. 1995 May;39(5):1101–1106. doi: 10.1128/aac.39.5.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gatti G., Merighi M., Hossein J., Travaini S., Casazza R., Karlsson M., Cruciani M., Bassetti D. Population pharmacokinetics of dapsone administered biweekly to human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1996 Dec;40(12):2743–2748. doi: 10.1128/aac.40.12.2743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Girard P. M., Landman R., Gaudebout C., Olivares R., Saimot A. G., Jelazko P., Gaudebout C., Certain A., Boué F., Bouvet E. Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group. N Engl J Med. 1993 May 27;328(21):1514–1520. doi: 10.1056/NEJM199305273282102. [DOI] [PubMed] [Google Scholar]
  11. Hansen I., Lykkegaard Nielsen M., Heerfordt L., Henriksen B., Bertelsen S. Trimethoprim in normal and pathological human lung tissue. Chemotherapy. 1973 Oct;19(4):221–234. doi: 10.1159/000221459. [DOI] [PubMed] [Google Scholar]
  12. Ioannidis J. P., Cappelleri J. C., Skolnik P. R., Lau J., Sacks H. S. A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens. Arch Intern Med. 1996 Jan 22;156(2):177–188. [PubMed] [Google Scholar]
  13. Lee B. L., Medina I., Benowitz N. L., Jacob P., 3rd, Wofsy C. B., Mills J., 5th Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Evidence of drug interactions. Ann Intern Med. 1989 Apr 15;110(8):606–611. doi: 10.7326/0003-4819-110-8-606. [DOI] [PubMed] [Google Scholar]
  14. Mallolas J., Zamora L., Gatell J. M., Miró J. M., Vernet E., Valls M. E., Soriano E., SanMiguel J. G. Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine. AIDS. 1993 Jan;7(1):59–64. [PubMed] [Google Scholar]
  15. Martin M. A., Cox P. H., Beck K., Styer C. M., Beall G. N. A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients. Arch Intern Med. 1992 Mar;152(3):523–528. [PubMed] [Google Scholar]
  16. Mirochnick M., Michaels M., Clarke D., Breña A., Regan A. M., Pelton S. Pharmacokinetics of dapsone in children. J Pediatr. 1993 May;122(5 Pt 1):806–809. doi: 10.1016/s0022-3476(06)80033-8. [DOI] [PubMed] [Google Scholar]
  17. Opravil M., Joos B., Lüthy R. Levels of dapsone and pyrimethamine in serum during once-weekly dosing for prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis. Antimicrob Agents Chemother. 1994 May;38(5):1197–1199. doi: 10.1128/aac.38.5.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Podzamczer D., Santín M., Jimenez J., Casanova A., Bolao F., Gudiol G. R. Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients. AIDS. 1993 Apr;7(4):501–506. doi: 10.1097/00002030-199304000-00008. [DOI] [PubMed] [Google Scholar]
  19. Rennard S. I., Basset G., Lecossier D., O'Donnell K. M., Pinkston P., Martin P. G., Crystal R. G. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1985) 1986 Feb;60(2):532–538. doi: 10.1152/jappl.1986.60.2.532. [DOI] [PubMed] [Google Scholar]
  20. Slavin M. A., Hoy J. F., Stewart K., Pettinger M. B., Lucas C. R., Kent S. J. Oral dapsone versus nebulized pentamidine for Pneumocystis carinii pneumonia prophylaxis: an open randomized prospective trial to assess efficacy and haematological toxicity. AIDS. 1992 Oct;6(10):1169–1174. [PubMed] [Google Scholar]
  21. Stavola J. J., Noel G. J. Efficacy and safety of dapsone prophylaxis against Pneumocystis carinii pneumonia in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 1993 Aug;12(8):644–647. doi: 10.1097/00006454-199308000-00004. [DOI] [PubMed] [Google Scholar]
  22. Tocchetti A., Tambini R., Allegro A., Longoni E., Rinaldi E. Four different regimens for prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in HIV-infected patients. AIDS. 1994 Feb;8(2):272–274. doi: 10.1097/00002030-199402000-00021. [DOI] [PubMed] [Google Scholar]
  23. Torres R. A., Barr M., Thorn M., Gregory G., Kiely S., Chanin E., Carlo C., Martin M., Thornton J. Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis. Am J Med. 1993 Dec;95(6):573–583. doi: 10.1016/0002-9343(93)90352-p. [DOI] [PubMed] [Google Scholar]
  24. Whicher J. T., Price C. P., Spencer K. Immunonephelometric and immunoturbidimetric assays for proteins. Crit Rev Clin Lab Sci. 1983;18(3):213–260. doi: 10.3109/10408368209085072. [DOI] [PubMed] [Google Scholar]

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