Comparative Fasting Bioavailability of Two Letrozole 2.5-mg Tablets in Healthy Chinese Postmenopausal Women:An Open-Label,Randomized-Sequence, Single-Dose, Two-Way Crossover study
Background:Letrozole is an orally active aromatase inhibitor indicated for the treatment of postmenopausal women with breast cancer.Although the bioavailability and pharmacokinetic (PK) properties of letrozole have been examined in western populations and healthy Chinese men,a literature search did not identify any reports concerning the bioavailability and PK properties of letrozole in a population of healthy Chinese postmenopausal women.Objective:The study was designed to assess and compare the PK properties and bioequivalence of two 2.5-mg tablets ofletrozole:the newly developed generic formulation (test) and a branded formulation (reference)in healthy Chinese postmenopausal women.Methods:A single-dose,randomized,open-label,two-way crossover study was conducted in healthy Chinese postmenopausal women under fasting conditions.Eligible participants were randomly assigned to receive 1 tablet (2.5 mg each) of the test or reference formulation,followed by a 21-day washout period and administration of the altemate formulation.Plasma samples were collected before dosing and at 0.25,0.50,0.75,1.00,1.25,1.50,2.00,2.50,3.00,3.50,4.00,6.00,8.00,12.00,24.00,48.00,72.00,96.00,144.00,192.00 and 240.00 hours after dosing.Plasma concentrations of letrozole were analyzed with a LC-MS/MS method.The safety profile was evaluated by recording adverse events (AEs),assessed using physical examination,vital signs,spontaneous reporting,and clinical laboratory results.The two formulations were considered bioequivalent if the 90% CIs for the In-transformed rations of Cmax and AUC values were within the predetermined equivalence range (80%-125%).Results:A total of 30 healthy Chinese postmenopausal women were enrolled in this study; however,only the data from 29 subjects were included (mean ”SD” age,54.9 ”4.7” years; weight,56.4 ”4.6” kg; height,158.7 ”4.8”cm; BMI,22.4 ”1.4” kg/m2) in the PK and bioequivalence assessments due to serious adverse events (SAEs)occurred in one subject.The 90% CIs for the ln-transformed ratios of Cmax,AUC0-t,and AUC0-∞ were 99.55% to 115.17%,97.35% to 103.50%,and 97.29% to 103.96%,respectively.All values met the predetermined criteria for assuming bioequivalence.One subject (3.3%) withdrew from the study because of SAEs.Ten subjects (33.3%)reported a total of 13 mild AEs.The test drug and the reference drug were tolerated equally by subjects in this study.Conclusions:This single-dose (2.5 mg) study found that the test and reference formulations of letrozole tablet met the regulatory definition for assuming bioequivalence in these healthy fasted Chinese postmenopausal women.Both formulations were generally well tolerated in the population studied.Chinese Clinical Trials registration number:ChiCTR-TRC-11001457.
Letrozole bioequivalence pharmacokinetics LC-MS/MS Chinese postmenopausal women
Yi Liu Wanyu Feng Dafang Zhong Yi Fang Yifan Zhang Qian Wang Wei Yang Xiaoyan Chen Shah Jing Libo Zhao Lihui Wei Xiaoping Li
Department of Pharmacy, Peking University People”s Hospital, Beijing, 100044, People”s Republic of C Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People”s Republ Department of Gynecology, Peking University People”s Hospital, Beijing, 100044, People”s Republic of
国内会议
成都
英文
202-210
2012-10-26（万方平台首次上网日期，不代表论文的发表时间）