EFFECTS OF PROBENECID ON THE PHARMACOKINETICS AND ELIMINATION OF ACYCLOVIR IN HUMANS
EFFECTS OF PROBENECID ON THE PHARMACOKINETICS AND ELIMINATION OF ACYCLOVIR IN HUMANS
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DOI：
10.1128/aac.21.5.804
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发表时间：
1982-01-01
影响因子：
4.9
通讯作者：
LIETMAN, PS
中科院分区：
文献类型：
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作者：
LASKIN, OL;DEMIRANDA, P;LIETMAN, PS
研究了丙磺舒对阿昔洛韦在人体内的药代动力学和肾清除率的影响。3名肾功能正常的志愿者在口服丙磺舒（1 g）前后均给予阿昔洛韦（5 mg/kg）1 h静脉滴注。其动力学符合零级输注二室开放模型。丙磺舒给药后，从阿昔洛韦输注结束后1.0 h开始，所有时间点的平均阿昔洛韦浓度在统计学上均高于无丙磺舒给药的阿昔洛韦输注后相应的平均阿昔洛韦浓度。在不存在丙磺舒的情况下，肾清除率（248 . ±. 80 ml/min/1.73 m2）占总清除率的83%（300 ± 0.80 ml/min/1.73 m2）。69 ml/min/1.73 m2），并且几乎是估计的肌酸酐清除率（90 ± 0.69 ml/min/1.73 m2）的3倍。48 ml/min/1.73 m2）。丙磺舒给药后，肾清除率下降32%（248 - 168 ml/min/1.73 m2; P ≤ 0.001）。0.05），曲线下面积增加40%（91.3至127.6 nmol.h/ml; P < 0.05），终末血浆半衰期增加18%（2.3至2.7 h; P < 0.01）。尽管具有统计学显著性，但丙磺舒的影响可能仅具有有限的临床意义。阿昔洛韦主要通过肾清除、肾小球滤过和肾小管分泌消除;丙磺舒可抑制至少部分肾小管分泌。
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.