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Differential foetal development of the O‐ and N‐demethylation of codeine and dextromethorphan in man.
Author(s) -
Ladona MG,
Lindstrom B,
Thyr C,
DunRen P,
Rane A
Publication year - 1991
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1991.tb03902.x
Subject(s) - dextromethorphan , microsome , cytochrome p450 , chemistry , blot , pharmacology , dextrorphan , endocrinology , medicine , biology , biochemistry , enzyme , gene
1. Codeine and dextromethorphan were N‐demethylated in human foetal liver microsomes at high rates which were close to the activities in adult livers. In contrast, foetal liver microsomes did not catalyze the O‐demethylation of these drugs at mid‐gestation. 2. The metabolic data were in accordance with the absence of P450IID6 and the presence of P450 IIIA as determined by Western blotting with anti‐human P450 IID6 (MAb 114/2) and anti‐rat P450 IIIA (PCN 2‐13‐1/C2) monoclonal antibodies, respectively. 3. The inhibitory effects of midazolam and dehydroepiandrosterone support the contention that the N‐demethylase is a human foetal form of the cytochrome P450 IIIA family. Consistent with this we found that blotting with the MAb PCN 2‐13‐1/C2, which recognizes an epitope specific for the P450 III family, correlated well with the N‐demethylase activities.