UGT1A1*28 genotype affects the in-vitro glucuronidation of thyroxine in human livers.

Objective: L-thyroxine (T4), the most widely used drug for hypothyroidism, undergoes glucuronidation by UDP-glucuronosyltransferases. Clinical evidence obtained after the administration of anticonvulsants suggest that glucuronidation may play an important role in T4 homeostasis in humans. The aims of this study were to determine the T4 glucuronidation ability of all commercially available human UGTs, and investigate the relationship between genetic polymorphisms in UGT1A1 and UGT1A9 and T4 glucuronidation in human livers.

Effects of green tea compounds on irinotecan metabolism.

The effects of green tea compounds on the metabolism of irinotecan have never been investigated. We aimed to study whether catechins [(-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC), (-)-epicatechin] affect the inactivation metabolism of irinotecan into 7-ethyl-10-[4-N-(1-piperidino)-1-amino]carbonyloxycamptothecin (NPC) (by CYP3A4) and 7-ethyl-10-hydroxycamptothecin (SN-38) into 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) (by UGT1A1). Human liver microsomes, hepatocytes and Hep G2 cells were incubated with catechins and treated with irinotecan and/or SN-38.

Study of the genetic determinants of UGT1A1 inducibility by phenobarbital in cultured human hepatocytes.

UGT1A1 is induced by phenobarbital. We investigated whether three common UGT1A1 variants are associated with the variability in UGT1A1 inducibility. Human hepatocytes were incubated with 2 mM phenobarbital for 2 and 6 days followed by 5 microM SN-38 (1 h), a UGT1A1 probe.