Fujita Ai, Hayamizu Kengo, Yoshihara Tatsuya, Zaitsu Masayoshi, Shiraishi Fumie, Arima Hisatomi, Matsuo Kazumasa, Shiokawa Kanako, Setoguchi Hidekazu, Sasaguri Toshiyuki
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Anesthesiology, Chihaya Hospital, Chihaya 2-30-1, Higashi-ku, Fukuoka, Japan.
JA Clin Rep. 2018 Aug 13;4(1):59. doi: 10.1186/s40981-018-0196-8.
To examine whether sex and polymorphisms of cytochrome P450 (CYP) 2B6 and UDP-glucuronosyltransferase (UGT) 1A9 affect the difference between predicted and measured plasma propofol concentration during continuous infusion by target-controlled infusion.
Blood samples of 69 patients (48 men and 21 women) were obtained at 4 h after initial propofol infusion. Percentage performance error (PE) was calculated to assess the difference between measured and predicted propofol concentration. Regression coefficients (β) and 95% confidence intervals (CI) of sex and the polymorphisms of CYP2B6 and UGT1A9 for PE were, separately and mutually, estimated with linear regression. Covariates included age and body mass index in the minimal adjusted model, and additionally included clinical factors (mean blood pressure, heart rate, volume of intravenous fluid, surgical site, surgical position, and pneumoperitoneum) in the full adjusted model. PE was higher in men than in women (28.7% versus 10.5%, p = 0.015). Female sex was inversely associated with PE: the minimal adjusted β = - 8.84 (95% CI, - 16.26 to - 1.43); however, the fully adjusted β with clinical factors became not significant. The average of PE did not differ between polymorphisms of CYP2B6 and UGT1A9, and β of CYP2B6 516G>T polymorphisms mutually adjusted with female sex was not significant. Mean blood pressure, heart rate, and volume of intravenous fluid were independently associated with PE in the full adjusted model.
Under 4 h anesthesia with propofol target-controlled infusion in our population, sex differences appeared to exist in the propofol concentration, which might be largely mediated by clinical factors, such as hemodynamic status.
UMIN-CTR UMIN000009015 , Registered 1 October 2012.
研究细胞色素P450（CYP）2B6和尿苷二磷酸葡萄糖醛酸转移酶（UGT）1A9的性别及基因多态性是否会影响靶控输注持续输注丙泊酚期间预测血浆丙泊酚浓度与实测血浆丙泊酚浓度之间的差异。
在首次输注丙泊酚4小时后采集了69例患者（48例男性和21例女性）的血样。计算百分比性能误差（PE）以评估实测丙泊酚浓度与预测丙泊酚浓度之间的差异。通过线性回归分别和相互估计性别以及CYP2B6和UGT1A9基因多态性对PE的回归系数（β）和95%置信区间（CI）。在最小校正模型中协变量包括年龄和体重指数，在完全校正模型中还包括临床因素（平均血压、心率、静脉输液量、手术部位、手术体位和气腹）。男性的PE高于女性（28.7%对10.5%，p = 0.015）。女性性别与PE呈负相关：最小校正β = -8.84（95%CI，-16.26至-1.43）；然而，纳入临床因素后的完全校正β变得不显著。CYP2B6和UGT1A9基因多态性之间的PE平均值无差异，CYP2B6 516G>T基因多态性与女性性别相互校正后的β不显著。在完全校正模型中平均血压、心率和静脉输液量与PE独立相关。
在我们的研究人群中，丙泊酚靶控输注4小时麻醉期间，丙泊酚浓度似乎存在性别差异，这可能很大程度上由血流动力学状态等临床因素介导。
UMIN-CTR UMIN000009015，2012年10月1日注册。
