Formation of an antibacterial metabolite from a new macrolide compound 23-O-benzyl-5-mycaminosyl-tylonolide (TMC-101), by a hepatic microsomal drug-metabolizing enzyme system

Hironori Nakura, H. Ohi, T. Miura, T. Fujiwara, H. Ishizone, T. Yokoi, M. Kitada, T. Kamataki

Research output: Contribution to journalArticle

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Abstract

Upon incubation of 23-O-benzyl-5-mycaminosyl-tylonolide (TMC-101) with liver microsomes in the presence of a nicotinamide adenine dinucleotide phosphate-generating system, at least four metabolites were formed: two of them were also formed by an enzyme(s) in rat serum. One of the metabolites formed by liver microsomes possessed antibacterial activity comparable to TMC-101 as examined by bioautography using Micrococcus luteus ATCC 9341 as a tester strain. Incubation of TMC-101 with rat serum degraded most of the parent compound and did not form the active metabolite. The capacity of liver microsomes to produce the active metabolite was increased by pretreatment of rats with 3-methylcholanthrene, phenobarbital and polychlorinated biphenyl. The metabolite with the antibacterial activity was estimated not to be formed by the N-demethylation of TMC-101, and was chemically unstable.

Original languageEnglish
Pages (from-to)377-383
Number of pages7
JournalJournal of Pharmacobio-Dynamics
Volume14
Issue number7
Publication statusPublished - 1991
Externally publishedYes

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Macrolides
Liver Microsomes
Liver
Enzymes
Pharmaceutical Preparations
Micrococcus luteus
Methylcholanthrene
Polychlorinated Biphenyls
Phenobarbital
Serum
NADP
23-O-benzyl-5-mycaminosyl-tylonolide

ASJC Scopus subject areas

  • Pharmacology

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Formation of an antibacterial metabolite from a new macrolide compound 23-O-benzyl-5-mycaminosyl-tylonolide (TMC-101), by a hepatic microsomal drug-metabolizing enzyme system. / Nakura, Hironori; Ohi, H.; Miura, T.; Fujiwara, T.; Ishizone, H.; Yokoi, T.; Kitada, M.; Kamataki, T.

In: Journal of Pharmacobio-Dynamics, Vol. 14, No. 7, 1991, p. 377-383.

Research output: Contribution to journalArticle

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AU - Nakura, Hironori

AU - Ohi, H.

AU - Miura, T.

AU - Fujiwara, T.

AU - Ishizone, H.

AU - Yokoi, T.

AU - Kitada, M.

AU - Kamataki, T.

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AB - Upon incubation of 23-O-benzyl-5-mycaminosyl-tylonolide (TMC-101) with liver microsomes in the presence of a nicotinamide adenine dinucleotide phosphate-generating system, at least four metabolites were formed: two of them were also formed by an enzyme(s) in rat serum. One of the metabolites formed by liver microsomes possessed antibacterial activity comparable to TMC-101 as examined by bioautography using Micrococcus luteus ATCC 9341 as a tester strain. Incubation of TMC-101 with rat serum degraded most of the parent compound and did not form the active metabolite. The capacity of liver microsomes to produce the active metabolite was increased by pretreatment of rats with 3-methylcholanthrene, phenobarbital and polychlorinated biphenyl. The metabolite with the antibacterial activity was estimated not to be formed by the N-demethylation of TMC-101, and was chemically unstable.

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