TY - JOUR
T1 - Induction of polymorphic 4′‐hydroxylation of S‐mephenytoin by rifampicin.
AU - Zhou, HH
AU - Anthony, LB
AU - Wood, AJ
AU - Wilkinson, GR
PY - 1990/9
Y1 - 1990/9
N2 - Studies were performed in 13 healthy subjects to determine whether treatment with rifampicin results in induction of the metabolism of mephenytoin. Daily dosing with 600 mg rifampicin for 22 days caused a three to eightfold increase in the 0‐8 h urinary R/S ratio of mephenytoin following oral administration (100 mg) of racemic drug to extensive metabolizers of the anticonvulsant. This was accompanied by a 40 to 180% increase in the 0‐8 h urinary excretion of the 4′‐hydroxy metabolite. Four weeks after discontinuing rifampicin, both metabolic indices had returned to their baseline values. By contrast, rifampicin had no effect on either measures of metabolism in subjects of the poor metabolizer phenotype. Thus, it appears that the activity of the enzyme (P‐450 MP) mediating the genetically determined 4'‐hydroxylation of S‐ mephenytoin can be significantly modulated by enzyme inducing agents such as rifampicin and possibly environmental agents with a similar ability. 1990 The British Pharmacological Society
AB - Studies were performed in 13 healthy subjects to determine whether treatment with rifampicin results in induction of the metabolism of mephenytoin. Daily dosing with 600 mg rifampicin for 22 days caused a three to eightfold increase in the 0‐8 h urinary R/S ratio of mephenytoin following oral administration (100 mg) of racemic drug to extensive metabolizers of the anticonvulsant. This was accompanied by a 40 to 180% increase in the 0‐8 h urinary excretion of the 4′‐hydroxy metabolite. Four weeks after discontinuing rifampicin, both metabolic indices had returned to their baseline values. By contrast, rifampicin had no effect on either measures of metabolism in subjects of the poor metabolizer phenotype. Thus, it appears that the activity of the enzyme (P‐450 MP) mediating the genetically determined 4'‐hydroxylation of S‐ mephenytoin can be significantly modulated by enzyme inducing agents such as rifampicin and possibly environmental agents with a similar ability. 1990 The British Pharmacological Society
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U2 - 10.1111/j.1365-2125.1990.tb03799.x
DO - 10.1111/j.1365-2125.1990.tb03799.x
M3 - Article
C2 - 2223426
AN - SCOPUS:0025005022
SN - 0306-5251
VL - 30
SP - 471
EP - 475
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 3
ER -