Stability of meropenem and effect of 1 beta-methyl substitution on its stability in the presence of renal dehydropeptidase I

Author:

Fukasawa M1,Sumita Y1,Harabe E T1,Tanio T1,Nouda H1,Kohzuki T1,Okuda T1,Matsumura H1,Sunagawa M1

Affiliation:

1. Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.

Abstract

The stability of meropenem in the presence of renal dehydropeptidase I (DHP-I) varied extremely with the animal source of the enzyme. Meropenem, compared with imipenem, was rather easily hydrolyzed by DHP-Is from mice, rabbits, and monkeys, while it showed a higher resistance to guinea pig and beagle dog DHP-Is. In addition, meropenem was four times more resistant than imipenem to human DHP-I. The 1 beta-methyl substituent on carbapenems, i.e., meropenem and 1 beta-methyl imipenem, made them considerably more resistant to mouse and swine DHP-Is than the 1-unsubstituted derivatives are.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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