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

The objective of this study was to determine the pharmacokinetics of trimetrexate and dapsone in AIDS patients with moderate to severe pneumocystis pneumonia. Trimetrexate, leucovorin, and dapsone were administered for 21 +/- 3 days in the following doses: trimetrexate glucuronate, 45 mg/m(2); leucovorin, 20 mg/m(2); and dapsone, 100 mg daily. The pharmacokinetics of trimetrexate, dapsone, and dapsone's metabolite, monoacetyldapsone, were determined at three separate periods over the course of treatment. Serial blood samples were obtained over 24 hours after dosing and anaIyzed for trimetrexate, dapsone, and monoacetyldapsone, and pharmacokinetic parameters were determined. The mean parameters obtained for the early, mid-, and late collection 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 statistically significant changes in pharmacokinetics for trimetrexate or dapsone were observed over the 21 +/- 3 day course of treatment. The results suggest that there are no major interactions between trimetrexate and dapsone when administered together in acutely ill patients. Journal of Clinical Pharmacology, 1999;39:268-274 (C) 1999 the American College of Clinical Pharmacology.