The Effect of UGT2B7*2 Polymorphism on the Pharmacokinetics of OROS® Hydromorphone in Taiwanese Subjects

This open-label, single-center, phase I study (NCT1487564) investigated the effect of uridine diphosphate-glucuronosyltransferase2B7 (UGT2B7*2) genetic polymorphism (H268Y) on the pharmacokinetics (PK) and safety of a single, oral, 16-mg dose of OROS (R) hydromorphone and its metabolite in healthy Taiwanese subjects. Plasma concentrations of hydromorphone and hydromorphone-3-glucuronide were determined in 28 subjects. PK parameters calculated included maximum plasma concentration (C-max); time to reach maximum plasma concentration (t(max)); area under plasma concentration-time curve from 0-48hours (AUC(0-48h)) and 0-infinite time (AUC); and hydromorphone-3-glucuronide:hydromorphone metabolic ratio (R-M). Mean plasma concentrations of hydromorphone and hydromorphone-3-glucuronide reached a maximum between 12-18hours and 18-21hours, respectively. No clear trend in PK parameters and no clinically significant differences in the incidence of treatment-emergent adverse events (TEAEs) were observed among different UGT2B7 genotypes. Our study found UGT2B7 polymorphism had no apparent effect on PK of OROS (R) hydromorphone; hydromorphone was well tolerated in pain-free volunteers when coadministered with naltrexone.