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峭，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（r^2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AUG0→∞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。

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 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.