利丙双卡因乳膏在中国健康受试者中的生物等效性研究  

Bioavailability study of lidocaine and prilocaine cream in Chinese healthy volunteers

作　　者：谢斌 刘杰 陈新民 杨沛欣 葛晓蕾 钟克凤 吴健龙 陈亚军[2] XIE Bin;LIU Jie;CHEN Xin-min;YANG Pei-xin;GE Xiao-lei;ZHONG Ke-feng;WU Jian-long;CHEN Ya-jun(Zhuhai Rundu Pharmaceutical Co.Ltd.Zhuhai 519041,Guangdong Province,China;Department of Pharmacy,Wuhan University of Science and Technology,Wuhan 430065,Guangdong Province,China)

机构地区：[1]珠海润都制药股份有限公司,广东珠海519041 [2]武汉科技大学药学系,湖北武汉430065

出　　处：《中国临床药理学杂志》2022年第3期249-253,258,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价利丙双卡因乳膏受试制剂和参比制剂在中国健康受试者中的生物等效性。方法用单剂量、开放性、双周期、双序列、交叉、随机设计。本次研究共40例健康受试者入组(空腹),每周期于受试者双腿正面均匀涂抹受试制剂或参比制剂60 g/400 cm^(2),清洗期为14 d。用液相色谱-串联质谱法测定人血浆中利多卡因和丙胺卡因的浓度,用WinNonlin 6.4版软件计算主要药代动力学参数,并评估2种制剂的生物等效性。结果在受试者双腿涂抹等量受试制剂和参比制剂后,血浆中利多卡因的主要药代动力学参数:C_(max)分别为(179.78±93.10)和(182.89±92.68)ng·mL^(-1),AUC_(0-t)分别为(1676.05±726.76)和(1657.15±673.00)ng·mL^(-1)·h,AUC_(0-∝)分别为(1691.72±724.67)和(1671.50±671.65)ng·mL^(-1)·h;丙胺卡因的主要药代动力学参数:C_(max)分别为(97.75±47.74)和(105.89±51.29)ng·mL^(-1),AUC_(0-t)分别为(793.40±327.87)和(825.63±324.61)ng·mL^(-1)·h,AUC_(0-∞)分别为(810.64±329.11)和(843.79±326.57)ng·mL^(-1)·h。2种制剂的C_(max)、AUC_(0-t)及AUC_(0-∞)经对数转换后的90%置信区间:利多卡因分别为93.10%~107.25%,97.03%~107.59%和97.20%~107.56%;丙胺卡因分别为87.70%~101.24%,92.02%~102.85%和92.08%~102.68%。结论在空腹条件下,单次使用利丙双卡因乳膏受试制剂和参比制剂均具有生物等效性。Objective To evaluate the bioequivalence of test preparation and reference preparation of lidocaine-prilocaine cream in Chinese healthy subjects.Methods A single-dose,open-label,two-sequence and two-period crossover clinical trial design was carried out in 40 healthy subjects under fasting condition.Either test preparation or reference preparation was evenly applied on the front of both legs of the subjects using a dose of 60 g/400 cm^(2) with a washing period of 14 days.The plasma concentrations of lidocaine and prilocaine were determined by LC-MS/MS.The pharmacokinetic parameters including C_(max),AUC_(0-t) and AUC_(0-∞) were calculated by WinNonlin(Version 6.4).The 90%confidence intervals(CIs)of the geometric mean ratio of C_(max),AUC_(0-t) and AUC_(0-∞) were calculated for bioequivalence assessment.Results After a single dose,the main pharmacokinetic parameters of lidocaine in test and reference preparations:C_(max) were(179.78±93.10)and(182.89±92.68)ng·mL^(-1),AUC_(0-t) were(1676.05±726.76)and(1657.15±673.00)ng·mL^(-1)·h,AUC_(0-∞) were(1691.72±724.67)and(1671.50±671.65)ng·mL^(-1)·h,respectively.The main pharmacokinetic parameters of prilocaine in test and reference preparations:C_(max) were(97.75±47.74)and(105.89±51.29)ng·mL^(-1),AUC_(0-t) were(793.40±327.87)and(825.63±324.61)ng·mL^(-1)·h,AUC_(0-∞) were(810.64±329.11)and(843.79±326.57)ng·mL^(-1)·h,respectively.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t) and AUC_(0-∞) for lidocaine were 93.10%-107.25%,97.03%-107.59%and 97.20%-107.56%,respectively,while these parameters for prilocaine were 87.70%-101.24%,92.02%-102.85%and 92.08%-102.68%,respectively.Conclusion The test preparation is bioequivalent to the reference preparation in Chinese healthy subjects under fasting condition.

关 键 词：利多卡因 丙胺卡因 生物等效性 药代动力学 空腹 液相色谱-串联质谱法 

分 类 号：R986[医药卫生—药品]