左卡尼汀咀嚼片的人体药动学及生物等效性

Bioequivalence and pharmacokinetics of L-carnitine chewable tablets in healthy volunteers

目的建立人血浆中左卡尼汀的LC-MS／MS测定方法，并研究健康受试者口服左卡尼汀咀嚼片后的药动学和相对生物利用度。方法采用双周期随机交叉试验设计。分别给予18名男性健康受试者左卡尼汀试验制剂或参比制剂2g，运用LC-MS／MS法检测血浆中药物浓度，运用DAS Ver 2．0计算药动学参数，进行生物等效性判定。结果参比制剂与试验制剂的主要药动学参数t1/2、σmax、tmax、AUC0→24h和AUC-→∞分别为（24．2±8．9）和（22．8±11．0）h，（15．8±3．8）和（14．9±3．8）ug·mL^-1，（4．8±0．7）和（4．4±1．1）h，（253．0±56．9）和（246．2±57．8）ug·mL^-1，（511．2±154．3）和（512．9±218．0）ug·mL^-1。其药动学参数的计算未校正内源性左卡尼汀的血浆浓度。试验制剂的相对生物利用度为（97．9±12．4）％（91．9％～102．6％）。结论检测方法简便、准确、灵敏。检测结果表明左卡尼汀两种制剂生物等效。

[ABSTRACT] A/M To determine L-carnitine levels in human plasma by LC-MS/MS and to study the bioequivalence and pharmacokinetics of reference and test L-camitine formulations. METHODS A double-phased stochastical crossover study was designed. Eighteen healthy volunteers were given a single dose of 2 g L-camitne of reference and test formulations individually. The drug in plasma was detected by LC-MS/MS. DAS 2.0 software was utilized to determine the pharmacokinetic parameters and relative bioavailability. RESULTS The main pharmacokinetic parameters t1/2 ,σmax, tmax,AUC0→24 h and AUC0→∞ of reference and test L-carnitine formulations were （24.2 ± 8.9） and （22.8 ± 11.0） h, （15.8±3.8） and （14.9± 3.8）ug·mL^-1, （4.8 ± 0.7） and （4.4± 1.1）h, （253.0 ± 56.9） and （246.2 ± 57.8）ug·mL^-1,（511.2± 154.3） and （512.9 ± 218.0）ug·mL^-1, respectively. The relative bioavailability of test chewable tablet was （97.9 ± 12.4）%（91.9% - 102.6%）. CONCLUSION The method is simple, accurate and sensitive, and two formulations are bioequivalent.