利巴韦林片在健康人体的生物等效性

Bioequivalence of ribavirin tablets in human plasma

目的评价利巴韦林2种片剂的生物等效性。方法20例男性健康受试者采用随机双交叉设计试验,用液相色谱-串联质谱法测定单剂量口服利巴韦林片受试制剂和参比制剂各300 mg后利巴韦林的血药浓度,所得数据采用软件BAPP2.0计算主要药动学参数。结果利巴韦林参比制剂与受试制剂主要药动学参数:t_(max)分别为(1.4±s 0.5)h,(1.9±1.0)h;c_(max)分别为(610±183)μg·L^(-1)和(598±194);μg·L^(-1),t(1/2)分别为(38±4)h和(36±5)h,AUC_(0～96)分别为(8 035±1795)μg·h·L^(-1)和(7 868±1 756)μg·h·L^(-1)。以AUC^(0～t)计算,利巴韦林受试制剂的平均相对生物利用度为(98±11)%,统计学结果表明2种制剂主要药动学参数c_(max)、AUC_(0～t)和t_(max)均无显著差异。结论本方法准确、专属、灵敏,2种制剂在人体内具有生物等效性。

AIM To develop a LC-MS/MS assay for the determination of ribavirin in human plasma and to investigate the pharmacokinetics and bioequivalence of 2 kinds ribavirin tablets for healthy volunteers. METHODS Test preparation （300 mg） and reference preparation （300 mg） were given individually as a single dose to 20 healthy male volunteers in randomized two-way crossover design. Plasma drug concentrations of ribavirin were determined by LC-MS/MS and presented as the major pharmacokinetic parameters. RESULTS The main pharmacokinetic parameters t1/2, tmax and cmax were （38 ± s 4） h, （1.4 ± 0.5） h and （610 ± 183） μg· L^-1 for the reference tablet; （36 ± 5） h, （1.9 ± 1.0） h and （598 ± 194） μg· L^-1 for the test tablet, respectively. The relative bioavalability of the test tablet was （98 ± 11） %. The results of variance analysis and two one-sided t-test showed that there were no significant difference between the reference and test formulations in the A UC and cmax. CONCLUSION The developed LC-MS/MS assay method is acurate, specific and sensitive and suitable for the pharmacokinetic research of ribavirin in human plasma.The results demonstrate that the two preparations are bioequivalent.