Pentamidine Pharmacokinetics in Patients with AIDS with Impaired Renal Function

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Abstract
In patients with normal renal function, pentamidine elimination half-life and plasma clearance (mean ± SD) were 6.22 ± 1.17hr 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/rnl) 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 <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.

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