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® 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 (Cmax); time to reach maximum plasma concentration (tmax); area under plasma concentration-time curve from 0-48 hours (AUC0-48 h) and 0-infinite time (AUC∞); and hydromorphone-3-glucuronide:hydromorphone metabolic ratio (RM). Mean plasma concentrations of hydromorphone and hydromorphone-3-glucuronide reached a maximum between 12-18 hours and 18-21 hours, 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® hydromorphone; hydromorphone was well tolerated in pain-free volunteers when coadministered with naltrexone.
Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.
Joris
J
Vandenbossche
Henry
H
Richards
Stephan
S
Francke
An
A
Van Den Bergh
Chih Cherng
CC
Lu
Monique A
MA
Franc
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D003692:Delayed-Action Preparations; D005260:Female; D005838:Genotype; D005965:Glucuronates / Q000493:pharmacokinetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D013624:Taiwan; D055815:Young Adult
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D005965:Glucuronates; C093624:hydromorphone-3-glucuronide; D009271:Naltrexone; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D004091:Hydromorphone
OROS® hydromorphone; extended release; genetic polymorphism; pharmacokinetics; phase 1; uridine diphosphate (UDP)-glucuronosyltransferase 2B7