利巴韦林含片的人体药动学及生物等效性研究  

Bioequivalence and pharmacokinetics of ribavirin buccal tablets in healthy volunteers

作　　者：罗晨辉[1] 陈笑艳[2] 孙玉明[2] 于华玲[2] 蒋云[1] 仇宇[1] 钟大放[2] 周晓[1] 刘亚利[1] 

机构地区：[1]湖南省肿瘤医院临床药理基地 [2]沈阳药科大学药物代谢与药物动力学实验室

出　　处：《中国临床药理学与治疗学》2008年第2期169-173,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：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80mg,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2～500ng/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tmax、Cmax、t1/2、AUC0-72和AUC0→∞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AUC0-72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。AIM： To determine ribavirin in human plasma by an LC/MS/MS method and to study the bioequivalence and pharmacokineties of reference and test ribavirin formulations. METHODS： A double-phased stochastieal 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 LG/MS/MS. The phannaeokinetie parameters as well as relative bioavailability were measured. RESULTS： The calibration curve was linear within the range of 2 - 500 ng/mL （ r^2 = 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 tmax, Cmax, t1/2, AUC0-72 and AUC0→∞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 bueeal tablet was（ 106 ± 16）%. CONCLUSION： The method is more simple, more accurate and much more sensitive. There is no significant difference between the main pharmaeokinetie parmeters of two formulations of ribavirin （ P 〉 0.05）, they are bioequivalent.

关 键 词：利巴韦林 药动学 生物等效性 高效液相串联-色谱质谱联用色谱法 

分 类 号：R969.1[医药卫生—药理学]