Oxymorphone extended release does not affect CYP2C9 or CYP3A4 metabolic pathways

被引:49
作者
Adams, M
Pieniaszek, HJ
Gammaitoni, AR
Ahdieh, H
机构
[1] Endo Pharmaceut Inc, Clin Operat, Chadds Ford, PA 19317 USA
[2] SFBC New Drug Serv Inc, Kennett Sq, PA USA
[3] HPP Consulting & Serv Inc, Elkton, MD USA
关键词
CYP2C9; CYP3A4; opioid; oxymorphone extended release; drug interactions;
D O I
10.1177/0091270004271969
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Two 14-day, randomized, open-label, parallel-group studies examined the effects of extended-release (ER) oxymorphone on CYP2C9 or CYP3A4 metabolic activities in healthy subjects. On days -1, 7, and 14, subjects received either a CYP2C9 probe (tolbutamide 500 mg) or CYP3A4 probes (midozolam and [C-14 N-methyl]-erythromycin for the erythromycin breath test). Subjects were randomized to 5 groups: high-dose oxymorphone ER (3 x 20 mg q12h) + naltrexone (50 mg q24h); low-dose oxymorphone ER (10-20 mg q12h); rifampin (2 x 300 mg q24h), an inducer of CYP2G9 and CYP3A4 activities; naltrexone (50 mg q24h); or CYP probes alone (controls). Probe metabolism was significantly altered by rifampin on days 7 and 14 (P < .05), whereas probe metabolism was not significantly affected by low-dose oxymorphone ER or by high-dose oxymorphone ER Plus naltrexone. Oxymorphone ER exhibits a minimal potential for causing metabolic drug-drug interactions mediated by CYP2C9 or CYP3A4.
引用
收藏
页码:337 / 345
页数:9
相关论文
共 15 条
[1]   Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites: Results of a randomized crossover study [J].
Adams, MP ;
Ahdieh, H .
PHARMACOTHERAPY, 2004, 24 (04) :468-476
[2]   Adverse drug events in hospitalized patients - Excess length of stay, extra costs, and attributable mortality [J].
Classen, DC ;
Pestotnik, SL ;
Evans, RS ;
Lloyd, JF ;
Burke, JP .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 277 (04) :301-306
[3]  
EDDY NB, 1959, J PHARMACOL EXP THER, V125, P116
[4]  
*END PHARM INC, 2002, DAT FIL
[5]  
*END PHARM INC, 2001, DAT FIL
[6]  
FLOCKHART D, 2003, CYTOCHROME P450 DRUG
[7]   DRUG-RELATED MORBIDITY AND MORTALITY - A COST-OF-ILLNESS MODEL [J].
JOHNSON, JA ;
BOOTMAN, JL .
ARCHIVES OF INTERNAL MEDICINE, 1995, 155 (18) :1949-1956
[8]   Drug glucuronidation in clinical psychopharmacology [J].
Liston, HL ;
Markowitz, JS ;
DeVane, CL .
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 2001, 21 (05) :500-515
[9]   Drug interactions with patient-controlled analgesia [J].
Lötsch, J ;
Skarke, C ;
Tegeder, I ;
Geisslinger, G .
CLINICAL PHARMACOKINETICS, 2002, 41 (01) :31-57
[10]   Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide [J].
Madsen, H ;
Enggaard, TP ;
Hansen, LL ;
Klitgaard, NA ;
Brosen, K .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2001, 69 (01) :41-47