The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.

译文

:在单次口服20 mg氟西汀(作为盐酸盐)后,在24位男女健康受试者中比较了氟西汀胶囊(参考)和片剂(测试)的药代动力学和相对生物利用度。采用随机,交叉设计,每个剂量之间有2周的清除期。通过简单,准确和精确的HPLC方法分析给药前和至多192小时的各个适当时间点获得的血清样品的氟西汀和去甲氟西汀含量。方差分析,功效分析,90%置信区间(CI)和两个单方面试验用于药代动力学参数的统计分析。制剂的耐受性良好。氟西汀的log-Cmax和log-AUC(0-无穷大)的几何平均值之比的点估计分别为0.912和0.935,其中90%为0.838-0.992和0.857-1.020。去甲氟西汀的相应点估计分别为0.952(90%CI = 0.843-1.075)和0.904(90%CI = 0.807-1.013)。因为两个90%CI均为AUC(0-无穷大)。 FDA提议的80%至125%区间中包括氟西汀和去氟西汀的Cmax和Cmax几何平均比值,根据吸收率和吸收程度,认为测试药物(氟西汀片)与参考药(百忧解胶囊)具有生物等效性。

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