Pilot Study Examining the Frequency of Several Gene Polymorphisms Involved in Morphine Pharmacodynamics and Pharmacokinetics in a Morbidly Obese Population

被引:17
作者
Linares, Celia Lloret [2 ,3 ]
Hajj, Aline [4 ,5 ]
Poitou, Christine [2 ,6 ]
Simoneau, Guy [3 ]
Clement, Karine [2 ,6 ]
Laplanche, Jean Louis [4 ,5 ]
Lepine, Jean-Pierre [4 ]
Bergmann, Jean Francois [3 ]
Mouly, Stephane [3 ,4 ]
Peoc'h, Katell [1 ,4 ,5 ]
机构
[1] Hop Lariboisiere, Serv Biochim & Biol Mol, F-75010 Paris, France
[2] Hop La Pitie Salpetriere, Assistance Publ Hop Paris, Dept Nutr & Endocrinol, F-75013 Paris, France
[3] Hop Lariboisiere, Assistance Publ Hop Paris, Dept Internal Med, Unit Therapeut Res, F-75475 Paris 10, France
[4] Paris Cite Descartes Univ, Fac Pharm, Ctr Natl Rech Sci, Inst Natl Sante & Rech Med,U705,UMR 7157, F-75006 Paris, France
[5] Hop Lariboisiere, Assistance Publ Hop Paris, Dept Biochem & Mol Biol, F-75475 Paris 10, France
[6] Cordelier Res Ctr, Inst Natl Sante & Rech Med, U872, Team7, F-75006 Paris, France
关键词
Morphine; Pharmacogenetics; Obesity; OPRM1; ABCB1; COMT; Analgesia; MU-OPIOID-RECEPTOR; CATECHOL-O-METHYLTRANSFERASE; SINGLE-NUCLEOTIDE POLYMORPHISM; P-GLYCOPROTEIN EXPRESSION; SUBSTANCE DEPENDENCE; COMT GENE; FUNCTIONAL POLYMORPHISMS; RESPIRATORY DEPRESSION; BARIATRIC SURGERY; DRUG-TRANSPORTER;
D O I
10.1007/s11695-010-0143-x
中图分类号
R61 [外科手术学];
学科分类号
摘要
Morbidly obese patients are at significantly elevated risk of postsurgery complications and merit closer monitoring by health care professionals after bariatric surgery. It is now recognized that genetic factors influence individual patient's response to drug used in anesthesia and analgesia. Among the many drug administered by anesthetists, we focused in this pilot study on morphine, since morphine patient-controlled anesthesia in obese patients undergoing gastric bypass surgery is frequently prescribed. We examined the allelic frequency of three polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in patients with body mass index (BMI) > 40. One hundred and nine morbidly obese patients (BMI = 49.1 +/- 7.7 kg/mA(2)) were genotyped for three polymorphisms c.A118G of mu opioid receptor (OPRM1), c.C3435T of the P-glycoprotein gene (ABCB1), and p.Val158Met of catechol-O-methyltransferase gene (COMT). Allelic frequencies were 118G-0.22, C3435-0.55, and 158Met-0.5 in our whole population and 0.23, 0.5, and 0.47 in Caucasian population. Allelic frequencies did not differ according to gender. Mean BMI did no differ according to the allelic variant. OPRM1118G allele was more frequent in our population than in most previously described European populations. Since the concept of "personalized medicine" promises to individualize therapeutics and optimize medical treatment in term of efficacy and safety, especially when prescribing drugs with a narrow therapeutic index such as morphine, further clinical studies examining the clinical consequences of the OPRM1 c.A118G polymorphism in patients undergoing gastric bypass surgery are needed.
引用
收藏
页码:1257 / 1264
页数:8
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