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The effects of phenytoin (PHT) or phenobarbital (PB) comedication on the concentrations, concentration ratios, and level/dose ratios of carbamazepine (CBZ) and its metabolites were investigated. The hetero-induction effects of CBZ metabolism by PHT or PB were clearly demonstrated. Serum CBZ level/dose ratios in patients with CBZ polytherapy were decreased while CBZ-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11-dihydro-CBZ (CBZ-H) concentrations were increased as compared with those of patients receiving CBZ alone. The concentration ratios of CBZ-H/CBZ and CBZ-E/CBZ were also greater in patients receiving CBZ+PHT or CBZ+PB than in patients receiving CBZ alone. In addition, positive correlations between serum PHT concentration and CBZ-H/CBZ or CBZ-E/CBZ concentration ratios were observed. There were no significant differences in CBZ-H/CBZ-E concentration ratios, the free fractions of CBZ and its metabolites, and CBZ-E or CBZ-H level/dose ratios among the three groups of patients. Because this approach investigates the in vivo relation between the substrates and products of the enzymes involved in CBZ biotransformation, more detailed information about the drug interactions was obtained. The results suggest that the PHT has a potent induction effect on CBZ epoxidase, whereas PB is a moderate inducer.
H Liu, and
M R Delgado
September 1990,
Therapeutic drug monitoring,
H Liu, and
M R Delgado
August 1978,
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H Liu, and
M R Delgado
January 1986,
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H Liu, and
M R Delgado
February 2007,
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H Liu, and
M R Delgado
April 1981,
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H Liu, and
M R Delgado
March 1991,
Therapeutic drug monitoring,
H Liu, and
M R Delgado
March 1991,
Clinical pharmacokinetics,
H Liu, and
M R Delgado
January 1979,
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H Liu, and
M R Delgado
January 2006,
Chronobiology international,
H Liu, and
M R Delgado
April 1979,
Epilepsia,
