Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans
- 1 May 1982
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 21 (5), 804-807
- https://doi.org/10.1128/aac.21.5.804
Abstract
The effects of probenecid on the pharmacokinetics and renal clearance of acyclovir were studied in humans. Acyclovir (5 mg/kg) was given as a 1-h infusion to 3 volunteers with normal renal function both before and after oral administration of probenecid (1 g). The kinetics were well described by a 2-compartment open model with zero-order infusion. The mean acyclovir concentrations at all time points after 1.0 h from the end of acyclovir infusion following probenecid administration were statistically higher than the corresponding mean acyclovir concentrations following the acyclovir infusion without probenecid administration. In the absence of probenecid, the renal clearance (248 .+-. 80 ml/min per 1.73 m2) accounted for 83% of the total clearance (300 .+-. 69 ml/min per 1.73 m2) and was almost 3-fold greater than the estimated creatinine clearance (90 .+-. 48 ml/min per 1.73 m2). After probenecid administration, there was a 32% decline in renal clearance (248 to 168 ml/min per 1.73 m2; P .ltoreq. 0.05), a 40% increase in the area under the curve (91.3 to 127.6 nmol.h/ml; P < 0.05), and an 18% increase in the terminal plasma half-life (2.3 to 2.7 h; P < 0.01). Although statistically significant, these effects due to the influence of probenecid probably have only limited clinical importance. Acyclovir is eliminated predominantly by renal clearance, by glomerular filtration and tubular secretion; at least part of the tubular secretion may be inhibited by probenecid.This publication has 12 references indexed in Scilit:
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