Pharmacokinetic Evaluation of Anticonvulsants in a Patient with Porphyria

抄録

The aim of this study was to establish the appropriate regimen of anticonvulsants for a female patient with porphyria by pharmacokinetic evaluation of the influence of anticonvulsants on porphyria. The pharmacokinetics of phenytoin, carbamazepine, clonazepam, and clobazam were estimated by the Bayesian method. The urinary 6β-hydroxycortisol/cortisol (6β-0HF/F) ratio was also evaluated as an index of hepatic CYP3A4 induction.
The phenytoin concentrations in the toxic area fitted the predicted value for CYP2C9^* 1/^*3 better than that for CYP2C9^*1/^*1 (her genotype). The concomitant phenytoin altered the clearance of carbamazepine considerably. The clearances of clonazepam and clobazam were not altered, although hepatic CYP3A4 induction was implied from the value of the urinary 6β-OHF/F ratio.
From the pharmacokinetic evaluations, the following were concluded: (1) phenytoin was not the proper medication for this patient, (2) carbamazepine can be used safely within a relatively small dose, 500 mg/day, (3) the combination of clonazepam and carbamazepine can be used, and (4) a concomitant small dose of clobazam with carbamazepine can also be used.