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

被引:7
作者
Vandenbossche, Joris [1 ]
Richards, Henry [2 ]
Francke, Stephan [3 ]
Van Den Bergh, An [1 ]
Lu, Chih Cherng [4 ]
Franc, Monique A. [3 ]
机构
[1] Johnson Johnson Pharmaceut Res & Dev, Beerse, Belgium
[2] Janssen Res & Dev LLC, Titusville, NJ USA
[3] Janssen Res & Dev LLC, Raritan, NJ USA
[4] Triserv Gen Hosp, Dept Anesthesiol, Natl Def Med Ctr, Taipei, Taiwan
关键词
extended release; genetic polymorphism; OROS (R) hydromorphone; pharmacokinetics; phase; 1; uridine diphosphate (UDP)-glucuronosyltransferase 2B7; GLUCURONOSYLTRANSFERASE; 2B7; UGT2B7; GENETIC POLYMORPHISMS; VALPROIC ACID; CHRONIC PAIN; PREVALENCE; GLUCURONIDATION; EXPRESSION; OPIOIDS; ASSOCIATION; CLEARANCE;
D O I
10.1002/jcph.305
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1170 / 1179
页数:10
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