文章基本信息

标题：Quantitative Evaluation of Effect of Renal Failure on the Pharmacokinetics of Panipenem in Rats
本地全文：下载
作者：Naoyuki Tajima ; Masako Soma ; Hitoshi Ishizuka 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2005
卷号：28
期号：11
页码：2170-2172
DOI：10.1248/bpb.28.2170
出版社：The Pharmaceutical Society of Japan
摘要：The pharmacokinetics of panipenem in experimental renal failure animal models was investigated in order to identify the appropriate covariates affecting the pharmacokinetic behavior. Panipenem and betamipron were administered intravenously to rats with a variety of renal failures, such as nephritis induced by glycerol, gentamicin, uranium and antiserum against glomerular basement membrane as well as 5/6 subtotal nephrectomy. Panipenem in plasma and urine was determined and pharmacokinetic analysis was performed using a one-compartment open model. The elimination half-life prolonged and total body clearance, renal clearance ( CL _R) and renal excretion ratio were decreased according to the renal function, i.e. control>glycerol>anti-GBM=gentamicin>nephrectomy=uranium in order. However, distribution volume was consistent in all models. CL _R showed strong positive correlation with the glomerular filtration rate in spite of a weak correlation with the reciprocal of blood urea nitrogen. However, no obvious correlation was observed with secretory clearance of N -1-methylnicotinamide. This preliminary information based on animal model might be useful for designing pharmacokinetic studies in special population at early stage of new drug development.
关键词：panipenem;pharmacokinetics;renal failure;experimental animal model;rat