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Effects of genetic polymorphisms of OPRM1, ABCB1, CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients.

International journal of clinical pharmacology and therapeutics (2013-04-06)
Kye-Min Kim, Ho-Sook Kim, Se Hun Lim, Soon Ho Cheong, Eun-Jung Choi, Hyun Kang, Hey-Ran Choi, Jin-Woo Jeon, Jun Heum Yon, Minkyung Oh, Jae-Gook Shin
ABSTRACT

Fentanyl, a μ-opioid receptor agonist, is a substrate of P-glycoprotein. Its metabolism is catalyzed by CYP3A4 and CYP3A5. The aim of this study was to investigate the association between postoperative fentanyl consumption and genetic polymorphisms of μ-opioid receptor (OPRM1), ABCB1 (gene encoding P-glycoprotein), CYP3A4 and CYP3A5 in Korean patients. 196 female patients scheduled to undergo total abdominal hysterectomy or laparoscopic assisted vaginal hysterectomy under general anesthesia were enrolled in this study. Intravenous patient-controlled analgesia with fentanyl was provided postoperatively. Cumulative fentanyl consumption was measured during the first 48 hours postoperatively. The severity of pain at rest was assessed with the visual analogue scale. OPRM1 118A>G, ABCB1 2677G>A/T, ABCB1 3435C>T, CYP3A4*18 and CYP3A5*3 variant alleles were genotyped. The effects of genetic and non-genetic factors on fentanyl requirements were evaluated with multiple linear regression analysis. The 24-hour cumulative fentanyl doses were significantly associated with pain core, weight and type of surgery (p < 0.05). The 48-hour cumulative fentanyl doses were significantly associated with pain score, type of surgery and history of PONV or motion sickness (p < 0.05). Genetic polymorphisms were not associated with fentanyl requirements. In Korean gynecologic patients, no association was found between genetic factors and postoperative fentanyl consumption.

MATERIALS
Product Number
Brand
Product Description

Supelco
Fentanyl solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Fentanyl citrate salt
Supelco
Fentanyl solution, 100 μg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®