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Antipyrine metabolite kinetics in healthy human volunteers during multiple dosing of phenytoin and carbamazepine.
Author(s) -
Shaw PN,
Houston JB,
Rowland M.,
Hopkins K.,
Thiercelin JF,
Morselli PL
Publication year - 1985
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.1365-2125.1985.tb05119.x
Subject(s) - carbamazepine , phenytoin , anticonvulsant , metabolite , dosing , pharmacokinetics , pharmacology , enzyme inducer , metabolism , chemistry , drug interaction , cytochrome p450 , drug , drug metabolism , medicine , epilepsy , endocrinology , enzyme , biochemistry , psychiatry
Antipyrine total clearance and the formation clearance of its major metabolites were studied in normal, healthy male volunteers before and after multiple dosing for approximately three weeks with phenytoin (six subjects) and carbamazepine (six subjects). Total antipyrine clearance increased on average by 91% after phenytoin dosing and by 61% after carbamazepine and individual increases correlated well with mean plasma concentrations of the anti‐epileptic drug. The increase in total clearance resulted largely from increased formation clearances of the 4‐ hydroxy and 3‐hydroxymethylantipyrine metabolites with minimal effect on the norantipyrine pathway, following treatment with both enzyme‐ inducing drugs. It is concluded that both phenytoin and carbamazepine have similar effects on antipyrine metabolism and that these effects are mediated by induction of specific forms of cytochrome P450.