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The disposition and metabolic fate of14C-meropenem in man

 

作者: HarrisonM. P.,   HaworthS. J.,   MossS. R.,   WilkinsonD. M.,   FeatherstoneA.,  

 

期刊: Xenobiotica  (Taylor Available online 1993)
卷期: Volume 23, issue 11  

页码: 1311-1323

 

ISSN:0049-8254

 

年代: 1993

 

DOI:10.3109/00498259309059441

 

出版商: Taylor&Francis

 

数据来源: Taylor

 

摘要:

1. The metabolism and pharmacokinetics of14C-meropenem were studied in five volunteers who received 0-5 g (40μCi) of the radiolabelled drug by i.v. infusion.2. The maximum concentration of drug in plasma was 27±2μg/ml (70μM) corresponding to 98% of plasma radioactivity at the end of a 30 min infusion. The elimination half-life for meropenem in plasma was 1 h and meropenem remained the major radioactive component up to 6 h, but represented a decreasing proportion of the plasma radioactivity with time. One metabolite (the ring-open lactam) accounted for most of the remaining plasma radioactivity. The maximum concentration of metabolite was 1±0.1μg/ml and the concentration of total radioactivity decreased to 2% of the peak value by 8 h.3. Over the 5 days of the study, urinary excretion of radioactivity accounted for 99±0.5% dose, most of which was recovered in the first 8 h. There was negligible excretion in faeces.4. Structural confirmation of the drug-related components in urine was accomplished by h.p.l.c.-mass spectrometry. Meropenem accounted for 71±2% dose of14C and the ring-open lactam metabolite for most of the remainder, no other metabolites were detected.5. Meropenem was the major radioactive component in urine up to 8 h after dosing and is therefore remarkably stable to human renal dehydropeptidase (DHP-1) compared with other carbapenems in clinical use.

 

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