PHARMACOKINETICS OF INTRAVENOUS PENTAMIDINE IN PATIENTS WITH NORMAL RENAL-FUNCTION OR RECEIVING HEMODIALYSIS

The pharmacokinetics of intravenous pentamidine were studied in 10 patients with normal renal function (group 1), 9 volunteer subjects without Pneumocystis carinii pneumonia who were receiving maintenance hemodialysis (group 2), and 5 patients with normal or mildly abnormal renal function (group 3) after the last dose of therapy. The concentration-time data were best represented by a three-compartment model. The peak plasma concentration, plasma clearance, and elimination half-life ranged from 249 +/- 80 to 227 +/- 110 ng/ml, 268 +/- 70 to 329 +/- 58 1/h, and 29 +/- 25 to 118 +/- 119 h, respectively, in groups 1 and 2. In group 1, trough concentration increased progressively (linear regression: y = 4.4x; r = .91, P = .001) without achieving steady state, and the renal clearance-to-plasma clearance ratio was 2.1% +/- 0.01%. In group 3, the elimination half-life after the last dose was 12.0 +/- 2.3 days. The elimination half-life of pentamidine was long and accumulation occurred with daily dosing even in patients with normal renal function. Dose adjustment is not recommended for renal impairment as renal clearance accounts for a small fraction (2.1%) of plasma clearance.