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The effect of UGT2B7*2 polymorphism on the pharmacokinetics of OROS® hydromorphone in Taiwanese subjects
Author(s) -
Vandenbossche Joris,
Richards Henry,
Francke Stephan,
Van Den Bergh An,
Lu Chih Cherng,
Franc Monique A.
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.305
Subject(s) - hydromorphone , ugt2b7 , pharmacokinetics , cmax , pharmacology , metabolite , glucuronide , active metabolite , chemistry , medicine , anesthesia , glucuronidation , opioid , biochemistry , receptor , enzyme , microsome
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 (C max ); time to reach maximum plasma concentration (t max ); area under plasma concentration‐time curve from 0–48 hours (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 12–18 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.