Pharmacokinetics of trimetrexate and dapsone in AIDS patients with Pneumocystis carinii pneumonia

The objective of this study was to determine the pharmacokinetics of trimet rexate and dapsone in AIDS patients with moderate to severe pneumocystis pn eumonia. Trimetrexate, leucovorin, and dapsone were administered for 21 +/- 3 days in the following doses: trimetrexate glucuronate, 45 mg/m(2); leuco vorin, 20 mg/m(2); and dapsone, 100 mg daily. The pharmacokinetics of trime trexate, dapsone, and dapsone's metabolite, monoacetyldapsone, were determi ned at three separate periods over the course of treatment. Serial blood sa mples were obtained over 24 hours after dosing and anaIyzed for trimetrexat e, dapsone, and monoacetyldapsone, and pharmacokinetic parameters were dete rmined. The mean parameters obtained for the early, mid-, and late collecti on periods were the following: trimetrexate: t(1/2) = 8.29, 9.15 10.00 hr; AUC = 16.85, 22.38, 24.49 mg.hr/l;Cl = 5.58, 4.14, 3.96 l/hr, respectively DDS: t(1/2) = 14.99, 26.59, 15.13 hr; AUC = 30.60, 35.29, 36.08 mg.hr/l; Cl = 3.82, 3.49, 3.01 l/hr, respectively. Monoacetyldapsone: t(1/2) = 20.25, 18.66, 26.32 hr; AUC = 24.05, 24.06, 23.86 mg.hr/l, respectively. No statis tically significant changes in pharmacokinetics for trimetrexate or dapsone were observed over the 21 +/- 3 day course of treatment. The results sugge st that there are no major interactions between trimetrexate and dapsone wh en administered together in acutely ill patients. Journal of Clinical Pharm acology, 1999;39:268-274 (C) 1999 the American College of Clinical Pharmaco logy.