Zhang Mengyu, Jin Ying, Yuan Xueying, He Chaoqun, Han Mei, Tu Faping, Wang Zhenlei
Department of Pharmacy, NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
Clinical Trial Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
Clin Pharmacokinet. 2025 Jun 4. doi: 10.1007/s40262-025-01510-7.
Obesity can alter the physiological profile of individuals, potentially impacting the pharmacokinetics of anesthetic agents. This study compared the pharmacokinetic profiles of lidocaine and its metabolites between obese patients and normal-weight patients following a single intravenous bolus during surgical operation, to inform dosing strategies for the obese Chinese population.
Twenty-nine obese patients scheduled for laparoscopic sleeve gastrectomy and 29 normal-weight patients for laparoscopic cholecystectomy were enrolled. Lidocaine (2%, 1.5 mg/kg) was administered intravenously to obese patients and normal-weight patients on the basis of adjusted body weight (ABW) and total body weight, respectively. Plasma samples were collected to analyze the pharmacokinetic profiles of lidocaine and its metabolites. Adverse events (AEs) were recorded throughout the study.
Obese patients had a significantly longer half-life for lidocaine (2.27 ± 0.69 h vs 0.94 ± 0.16 h, p < 0.0001), a higher volume of distribution (105 ± 27.3 L vs 54.9 ± 14.0 L, p < 0.0001), and a lower clearance (33.6 ± 9.08 L/h vs 40.5 ± 8.67 L/h, p = 0.008) compared to normal-weight patients. Although exposure to lidocaine was similar between groups within 2 hours, obese patients had lower metabolite concentrations due to decreased metabolic capacity. The plasma concentrations in all patients remained below the toxic concentration of 5 μg/mL, and no serious lidocaine-related AEs were reported.
Obesity significantly affects the pharmacokinetics of lidocaine and its active metabolites, and administering lidocaine intravenously via ABW is safe and reasonable for obese patients.
ChiCTR2200064980, 25 October 2022.
肥胖会改变个体的生理特征,可能影响麻醉药物的药代动力学。本研究比较了肥胖患者和正常体重患者在手术期间单次静脉推注利多卡因及其代谢产物后的药代动力学特征,以为肥胖中国人群的给药策略提供依据。
纳入29例行腹腔镜袖状胃切除术的肥胖患者和29例行腹腔镜胆囊切除术的正常体重患者。分别根据调整体重(ABW)和总体重,对肥胖患者和正常体重患者静脉注射利多卡因(2%,1.5 mg/kg)。采集血浆样本以分析利多卡因及其代谢产物的药代动力学特征。在整个研究过程中记录不良事件(AE)。
与正常体重患者相比,肥胖患者利多卡因的半衰期显著延长(2.27±0.69小时对0.94±0.16小时,p<0.0001),分布容积更高(105±27.3升对54.9±14.0升,p<0.0001),清除率更低(33.6±9.08升/小时对40.5±8.67升/小时,p=0.008)。尽管两组在2小时内利多卡因的暴露量相似,但由于代谢能力下降,肥胖患者的代谢产物浓度较低。所有患者的血浆浓度均保持在5μg/mL的中毒浓度以下,且未报告与利多卡因相关的严重不良事件。
肥胖显著影响利多卡因及其活性代谢产物的药代动力学,对肥胖患者通过ABW静脉注射利多卡因是安全合理的。
ChiCTR2200064980,2022年10月25日。