Effect of gender and race on the pharmacokinetics of pentamidine in HIV-infected patients

Objectives: We studied the effects of race and gender on the pharmacokinetics of intravenously administered pentamidine as women and minorities have been under-represented in earlier studies and the incidence of HIV and opportunistic infection is increasing in these groups. Patients and Methods: Twenty HIV-positive individuals (10 men and 10 women) were enrolled into a prospective study. Recruitment of 11 Black subjects (six men and five women) allowed for gender and race comparisons. A single dose of intravenous pentamidine, 4 mg/kg, was administered as a 2-hour infusion. Serial plasma and urine drug concentrations were measured using column chromatography (HPLC). Results: Gender and/or race had no effect on drug concentrations or pharmacokinetic parameters. Plasma concentrations at 2 (peak), 12, 24 and 48 hours were 573 +/- 432, 5.7 +/- 3.2, 2.9 +/- 1.5 and 1.4 +/- 1.0 mu g/L. The initial Volume of distribution (V-1) for the entire group was 0.11 +/- 0.12kl and the elimination half-life was 24.9 +/- 10.4 hours. The plasma and urinary clearances were 0.31 +/- 0.12 and 0.01 +/- 0.01 kl/h, and the renal clearance/plasma clearance ratio was 0.03 +/- 0.01. Conclusions: The pharmacokinetics of single-dose intravenous pentamidine in women and Black patients were not significantly different from those that have been previously published. Dosage guidelines and strategies to reduce toxicity, such as dose reduction (3 or 2 mg/kg/day) or alteration of the dose based upon renal function or plasma drug concentrations, are likely to be appropriate for women and Black patients.