Bas i s stud i es on the appropr i ate usage of c l i n i ca I med i c i ne : i so form specificity of the functional interaction between drug metabolizing enzymes and the individual differences

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Interaction between cytochP4so P450 CYPsA4YP3A4) and UDPglucuronosyltransferase(UGT) isoforms in COS cells was evidenced by an analysis using Fluorescence Resonance Energy Transfer. FurtCYPsA4YP3A4 affects the glucuronidation activity catalyzeUGTlAiGT1A7 and 1A3. However, the modifying effecCYPsA4YP3A4 differed between UGT isoforms. In addition, differences were also seen in the effecCYPsA4YP3AUGTlAiGT1A7 variants* 1,* 2 and* 3. Therefore, these results support the hypothesis that the interaction betCYPsA4YP3A4 and UGT is one of the determinants involved in the interindividual difference in glucuronidation. On the other hand, it is also suggested that some of the endogenous and foodderived compounds modulate UGT activity.