アクティブボード・２００９年１１月
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研究発表を行った学会；
・The International Symposium on Pharmacogenomics in Epilepsy
　２００９年１０月２４日（弘前）

タイトル；Effect of hepatic nuclear factor4α, pregnane X receptor and constitutive androstane receptor polymorphisms on the carbamazepine pharmacokinetics in Japanese epileptic patients.
　
発表者；　岡田　祐輔　氏
　　　（熊本大学　大学院医学薬学研究部　薬物治療学分野）

Abstract；
Background: Carbamazepine (CBZ) and other anticonvulsants induce drug-metabolizing enzymes and transporters through nuclear receptor-mediated mechanisms. However, the effect of common polymorphisms of nuclear receptors on the pharmacokinetics of anticonvulsants has remained unknown.
Methods: The association between the steady state CBZ concentrations to dose (C/D) ratio and hepatic nuclear factor4α (HNF4α) Met49Val, pregnane X receptor (PXR) C8055T and T11193C, and constitutive androstane receptor (CAR) Pro180Pro polymorphisms was evaluated in 194 Japanese patients treated with CBZ.
Results: Among 78 patients treated with CBZ monotherapy, HNF4α Val carriers had significantly higher C/D ratios than non-carriers (mean±SD, 0.021±0.009 vs 0.016±0.006 μg/ml/mg, P=0.046). Regarding PXR polymorphisms, the mean C/D ratios tended to be higher in the 8055CC or CT genotype than in the TT genotype (0.020μg/ml/mg and 0.019μg/ml/mg vs. 0.017μg/ml/mg, respectively, P=0.51) and also higher in the 11193TT or TC genotype than in the CC genotype. No association was observed between the CAR Pro180Pro polymorphism and the C/D ratio. Among all, including those with polytherapy, the mean C/D ratio was insignificantly higher in HNF4α Val carriers, but did not differ among the PXR or CAR genotypes.
Conclusion: To the best of our knowledge, this is the first report showing the association between a common polymorphism of HNF4α and the CBZ pharmacokinetics. The clinical relevance of the result should be investigated further.