利巴韦林含片的人体药动学及生物等效性研究

目的:建立人血浆中利巴韦林的HPLC-MS分析方法, 用以测定18 名健康男性受试者舌下含服不同厂家的利巴韦林含片后的血药浓度, 估算受试制剂和参比制剂的药动学参数, 评价两种制剂是否生物等效。方法:采用双周期随机交叉试验设计。分别给予18 名男性健康受试者试验制剂或参比制剂80 mg, 采集静脉血样, 血浆样品去蛋白后用HPLC/MS/MS 法检测药物浓度。计算药动学参数, 判定两制剂是否生物等效。结果:测定利巴韦林的线性范围为2 ~ 500 ng/mL (r² 为0.9944), 平均回收率>90 %, 日内RSD 和日间RSD 均<10 %。测得血浆中两种制剂的利巴韦林的主要药代动力学参数t_max 、C_max 、t _1/2 、AUC_{0 -72} 和AUC_0→∞分别为:(1.1 ±0.5) 、(1.1 ±0.4) h, (249±89) 、(232 ±65) ng/mL, (34 ±11) 、(34 ±11) h,(2828 ±1215) 、(2685 ±1096) ng^。h^。mL^-1, (3600 ±1568) 、(3416 ±1379) ng^。h^。mL^-1 。以AUC_{0 -72} 计算, 利巴韦林含片的相对生物利用度平均为(106±16) %。结论:本方法更简便、准确, 灵敏度得到很大提高。两种制剂的利巴韦林药代动力学参数无统计学差异, 具有生物等效性。

Bioequivalence and pharmacokinetics of ribavirin buccal tablets in healthy volunteers

AIM:To determine ribavirin in human plasma by an LC/MS/MS method and to study the bioequivalence and pharmacokinetics of reference and test ribavirin formulations.METHODS:A double-phased stochastical crossover study design was conducted.18 healthy volunteers were given a single dose of 80 mg ribavirin of reference and test formulations.The drug was extracted from collected plasma and analyzed by LC/MS/MS.The pharmacokinetic parameters as well as relative bioavailability were measured.RESULTS:The calibration curve was linearwithin the range of 2 - 500 ng/mL (r² =0.9944).The average recovery was more than 90 %.The average RSD within 3 days and between 3 days were all less than 10 %.The major pharmacokinetic parameters t_max 、C_max 、t _1/2 、AUC_{0 -72} and AUC_0~∞ of reference and test ribavirin formulations were (1.1 ±0.5) and (1.1 ±0.4) h, (249 ±89) and (232 ±65) ng/mL, (34 ±11) and (34 ±11) h, (2828 ±1215) and (2685 ±1096) ng^。h^。mL ^-1, (3600 ±1568) and (3416 ±1379) ng^。h^。mL ^-1.The relative bioavailability of test buccal tablet was(106 ±16) %. CONCLUSION:The method is more simple, more accurate and much more sensitive.There is no significant difference between the main pharmacokinetic parmeters of two formulations of ribavirin (P >0.05), they are bioequivalent.