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. 1994 May;38(5):1197–1199. doi: 10.1128/aac.38.5.1197

Levels of dapsone and pyrimethamine in serum during once-weekly dosing for prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.

M Opravil 1, B Joos 1, R Lüthy 1
PMCID: PMC188179  PMID: 8067765

Abstract

Concentrations of dapsone, monoacetyldapsone, and pyrimethamine were determined in 36 serum samples from human immunodeficiency virus-infected patients on prophylaxis with once-weekly administration of dapsone-pyrimethamine (200 mg of dapsone-75 mg of pyrimethamine). During day 1 after ingestion, median levels of 1,038 ng of dapsone per ml and 356 ng of pyrimethamine per ml were found. During days 6 to 7, the dapsone level fell to < 20 ng/ml in five of nine serum samples, but the pyrimethamine level remained elevated (125 ng/ml). Concurrent, but separately ingested, didanosine administration did not seem to decrease the drug concentrations.

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Selected References

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  1. Allegra C. J., Boarman D., Kovacs J. A., Morrison P., Beaver J., Chabner B. A., Masur H. Interaction of sulfonamide and sulfone compounds with Toxoplasma gondii dihydropteroate synthase. J Clin Invest. 1990 Feb;85(2):371–379. doi: 10.1172/JCI114448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allegra C. J., Kovacs J. A., Drake J. C., Swan J. C., Chabner B. A., Masur H. Activity of antifolates against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent. J Exp Med. 1987 Mar 1;165(3):926–931. doi: 10.1084/jem.165.3.926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broughton M. C., Queener S. F. Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs. Antimicrob Agents Chemother. 1991 Jul;35(7):1348–1355. doi: 10.1128/aac.35.7.1348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chamberland S., Kirst H. A., Current W. L. Comparative activity of macrolides against Toxoplasma gondii demonstrating utility of an in vitro microassay. Antimicrob Agents Chemother. 1991 May;35(5):903–909. doi: 10.1128/aac.35.5.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Derouin F., Chastang C. In vitro effects of folate inhibitors on Toxoplasma gondii. Antimicrob Agents Chemother. 1989 Oct;33(10):1753–1759. doi: 10.1128/aac.33.10.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Derouin F., Piketty C., Chastang C., Chau F., Rouveix B., Pocidalo J. J. Anti-Toxoplasma effects of dapsone alone and combined with pyrimethamine. Antimicrob Agents Chemother. 1991 Feb;35(2):252–255. doi: 10.1128/aac.35.2.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edstein M. D., Rieckmann K. H., Veenendaal J. R. Multiple-dose pharmacokinetics and in vitro antimalarial activity of dapsone plus pyrimethamine (Maloprim) in man. Br J Clin Pharmacol. 1990 Aug;30(2):259–265. doi: 10.1111/j.1365-2125.1990.tb03773.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Edstein M. Quantification of antimalarial drugs. II. Simultaneous measurement of dapsone, monoacetyldapsone and pyrimethamine in human plasma. J Chromatogr. 1984 May 11;307(2):426–431. [PubMed] [Google Scholar]
  10. Jones C. R., Ovenell S. M. Determination of plasma concentrations of dapsone, monoacetyl dapsone and pyrimethamine in human subjects dosed with maloprim. J Chromatogr. 1979 Jun 11;163(2):179–185. doi: 10.1016/s0378-4347(00)81461-9. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Lee H. S., Ti T. Y., Lee P. S., Yap C. L. Simultaneous estimation of serum concentrations of dapsone, monoacetyldapsone, and pyrimethamine in Chinese men on maloprim for malaria prophylaxis using reversed-phase high performance liquid chromatography. Ther Drug Monit. 1985;7(4):415–420. doi: 10.1097/00007691-198512000-00009. [DOI] [PubMed] [Google Scholar]
  13. May D. G., Porter J. A., Uetrecht J. P., Wilkinson G. R., Branch R. A. The contribution of N-hydroxylation and acetylation to dapsone pharmacokinetics in normal subjects. Clin Pharmacol Ther. 1990 Dec;48(6):619–627. doi: 10.1038/clpt.1990.204. [DOI] [PubMed] [Google Scholar]
  14. Metroka C. E., McMechan M. F., Andrada R., Laubenstein L. J., Jacobus D. P. Failure of prophylaxis with dapsone in patients taking dideoxyinosine. N Engl J Med. 1991 Sep 5;325(10):737–737. doi: 10.1056/nejm199109053251014. [DOI] [PubMed] [Google Scholar]
  15. Stein D. S., Stevens R. C., Terry D., Laizure S. C., Palte S., Lancaster D. J., Weems J. J., Williams C. L. Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1991 Sep;35(9):1705–1709. doi: 10.1128/aac.35.9.1705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Weiss L. M., Harris C., Berger M., Tanowitz H. B., Wittner M. Pyrimethamine concentrations in serum and cerebrospinal fluid during treatment of acute Toxoplasma encephalitis in patients with AIDS. J Infect Dis. 1988 Mar;157(3):580–583. doi: 10.1093/infdis/157.3.580. [DOI] [PubMed] [Google Scholar]
  17. Zuidema J., Hilbers-Modderman E. S., Merkus F. W. Clinical pharmacokinetics of dapsone. Clin Pharmacokinet. 1986 Jul-Aug;11(4):299–315. doi: 10.2165/00003088-198611040-00003. [DOI] [PubMed] [Google Scholar]

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