Pentamidine pharmacokinetics in patients with AIDS with impaired renal function.
In patients with normal renal function, pentamidine elimination half-life and plasma clearance (mean +/- SD) were 6.22 +/- 1.17 hr and 411 +/- 55 liters/hr, respectively. With creatinine clearances from 35 to 145 ml/min, neither the elimination half-life (P = .47) nor the plasma clearance (P = .40) was correlated with renal function. Plasma concentrations in patients receiving dialysis ranged between 5.9 and 582 ng/ml and appeared not to be significantly affected by dialysis. The number of prior doses and the elimination half-life estimated from the terminal slope were correlated (r = .81, P = .025), and the results suggested that the current assay technology is still not sensitive enough to detect true elimination half-life. Trough plasma concentrations ranged between 4.3 and 67.5 ng/ml (28.4 +/- 26.6 ng/ml) in patients who had received prior doses of pentamidine, a result suggesting that drug accumulation occurs with multiple dosing. The data suggest that dosage adjustments are not necessary with creatinine clearances of greater than 35 ml/min. Because multiple dosing leads to increased trough concentrations and drug accumulation, lower dose regimens may still be efficacious, yet associated with reduced toxicity.
Conte
J E
JE
School of Medicine, University of California, San Francisco 94143-0208.
Upton
R A
RA
Lin
E T
ET
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism*; D000328:Adult; D000578:Amidines / Q000493:pharmacokinetics*; D002648:Child; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010419:Pentamidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010530:Peritoneal Dialysis; D011446:Prospective Studies; D006435:Renal Dialysis
D000578:Amidines; D010419:Pentamidine