慶應義塾大学 · 医学
Hisakazu Ohtani教授の研究室は、主に薬物代謝酵素であるサイコクロムP450（CYP）の遺伝的多様性が薬物相互作用に与える影響を解明する研究を行っています。特にCYP3A4の遺伝子多型が、メカニズムに基づく阻害（MBI）のキネティクスにどのように影響するかを定量的に解析しています。また、食事中のコレステロールや脂肪酸の摂取が脂質代謝に与える影響についても、ハムスターを用いた実験的アプローチで研究を展開しています。
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The effects of dietary cholesterol and fatty acids on the plasma cholesterol level and rates of very low density lipoprotein (VLDL) cholesterol secretion and low density lipoprotein (LDL) transport through LDL receptors in the liver of the hamster were investigated. Increases of plasma VLDL- and LDL-cholesterol levels and VLDL-cholesterol secretion from hepatocytes were observed in animals fed a diet enriched with 0.1% cholesterol for 2 weeks in comparison with animals fed a control diet. The ad
In order to evaluate the arrhythmogenic potency of macrolide antibiotics in a quantitative manner, we analyzed the influence of clarithromycin (CAM), roxithromycin (RXM), and azithromycin (AZM) on Q-T intervals from pharmacokinetic and pharmacodynamic points of view and in comparison with the potency of erythromycin (EM) previously reported by us for rats. Male Sprague-Dawley rats were anesthetized, and CAM (6.6, 21.6, and 43.2 mg/kg of body weight/h), RXM (20 and 40 mg/kg/h), and AZM (40 and 10
Inhibition of cytochrome P450 (CYP) 3A4 is the major cause of drug-drug interactions (DDI). We have previously reported that the genetic variation of CYP3A4 significantly affected the inhibitory profiles of typical competitive inhibitors. In addition to competitive inhibition, some clinically significant DDI are attributable to mechanism-based inhibition (MBI). However, the differences in the MBI kinetics among CYP3A4 genetic variants remain to be characterized. In this study, we quantitatively
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