Stability of meropenem and effect of 1 beta-methyl substitution on its stability in the presence of renal dehydropeptidase I.
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.
Fukasawa
M
M
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Sumita
Y
Y
Harabe
E T
ET
Tanio
T
T
Nouda
H
H
Kohzuki
T
T
Okuda
T
T
Matsumura
H
H
Sunagawa
M
M
D000818:Animals; D004150:Dipeptidases / Q000378:metabolism*; D004285:Dogs; D004355:Drug Stability; D006168:Guinea Pigs; D006801:Humans; D006868:Hydrolysis; D015378:Imipenem / Q000493:pharmacokinetics; D008253:Macaca mulatta; D000077731:Meropenem; D051379:Mice; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine; D013845:Thienamycins / Q000493:pharmacokinetics*
D013845:Thienamycins; D015378:Imipenem; D004150:Dipeptidases; C038937:dipeptidase; D000077731:Meropenem