Pentamidine pharmacokinetics in patients with AIDS with impaired renal function |
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Authors: | J E Conte R A Upton E T Lin |
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Institution: | School of Medicine, University of California, San Francisco 94143-0208. |
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Abstract: | 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. |
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