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肾功能不全患者的头孢羟氨苄动力学

Cefadroxil kinetics in patients with renal insufficiency.

作者信息

Cutler R E, Blair A D, Kelly M R

出版信息

Clin Pharmacol Ther. 1979 May;25(5 Pt 1):514-21. doi: 10.1002/cpt1979255part1514.

Abstract

Kinetic parameters and bioavailability of cefadroxil were studied in 20 subjects with differing renal function as measured by endogenous creatinine clearance (CCr). Two subjects were on hemodialysis. After an overnight fast, each subject ingested two 500-mg capsules of cefadroxil. The peak serum concentration was variable (12 to 57 mg/L) and correlated inversely with the CCr. All but one patient had maximum absorption within 4 hr of ingestion and in most patients the peak was reached within the 2-hr sample. Urinary recovery within 48 hr was 45% to 106% when CCr greater than 8 ml/min. Even in patients with the most severe renal failure (CCr less than 10 ml/min), urine concentrations of cefadroxil were adequate to treat susceptible bacteria. The rate of oral absorption ka, was not affected by the state of renal function and was 0.76 +/- 0.50 hr-1. The apparent distribution volume (V d ext) was 0.28 +/- 0.09 L/kg. The plasma elimination rate was dependent on CCr wih a small fraction of drug being removed by nonrenal routes. Except in advanced renal failure, tubular secretion was present since renal clearance of cefadroxil exceeded CCr. The data suggest that little drug accumulation will occur with the usual 8- to 12-hr dosing schedule except when the CCr is less than 25 ml/min.

摘要

通过内生肌酐清除率(CCr)测定,在20名肾功能不同的受试者中研究了头孢羟氨苄的动力学参数和生物利用度。两名受试者接受血液透析。经过一夜禁食后,每位受试者口服两粒500毫克的头孢羟氨苄胶囊。血清峰值浓度各不相同(12至57毫克/升),且与CCr呈负相关。除一名患者外,所有患者在服药后4小时内达到最大吸收,大多数患者在2小时采样时达到峰值。当CCr大于8毫升/分钟时,48小时内尿液回收率为45%至106%。即使在最严重肾衰竭(CCr小于10毫升/分钟)的患者中,头孢羟氨苄的尿液浓度也足以治疗易感细菌。口服吸收速率常数ka不受肾功能状态影响,为0.76±0.50小时-1。表观分布容积(Vdext)为0.28±0.09升/千克。血浆消除率取决于CCr,一小部分药物通过非肾脏途径清除。除晚期肾衰竭外,由于头孢羟氨苄的肾清除率超过CCr,存在肾小管分泌。数据表明,除CCr小于25毫升/分钟外,按照通常的8至12小时给药方案几乎不会发生药物蓄积。

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