Yanping Liu, Yuping Ning, Yan Shi, Man Xu, Juanmin Tao, Yafen Dong, Jun Ma, Yan Qiu
{"title":"枸橼酸托法替尼片两种制剂在中国健康志愿者空腹和进食条件下的生物等效性和安全性:随机、开放标签、两阶段、单剂量、交叉试验","authors":"Yanping Liu, Yuping Ning, Yan Shi, Man Xu, Juanmin Tao, Yafen Dong, Jun Ma, Yan Qiu","doi":"10.1155/2024/7914586","DOIUrl":null,"url":null,"abstract":"<div>\n <p><i>Purpose</i>. To evaluate the bioequivalence of two different tofacitinib citrate tablets formulations among healthy Chinese subjects under fasting and fed conditions and to observe the safety of test preparation and reference preparation in healthy subjects. <i>Method</i>. This randomized, open-label, 2-period, crossover, bioequivalence study included 64 healthy Chinese subjects (fasting: <i>n</i> = 32, fed: <i>n</i> = 32). The subjects were assigned to receive a single 5-mg dose of the test or a reference tofacitinib citrate tablets. Blood samples were collected at predose and up to 24 hours after dosing. Area under the plasma concentration time curve from zero to the last measurable concentration (AUC<sub>0-<i>t</i></sub>), the area from time zero to infinite (AUC<sub>0-∞</sub>), and maximum plasma concentration (<i>C</i><sub>max</sub>) were used for bioequivalence assessment. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, from the time the subject receiving the test drug to the end of the last visit. <i>Results</i>. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 98.40–104.16% for AUC<sub>0-<i>t</i></sub>, 89.96–116.70% for <i>C</i><sub>max</sub>, and 98.50–104.15% for AUC<sub>0-∞</sub>. Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 93.65–101.60% for AUC<sub>0-<i>t</i></sub>, 90.06–109.15% for <i>C</i><sub>max</sub>, and 93.88–101.51% for AUC<sub>0-∞</sub>. There were no serious events. <i>Conclusion</i>. The 90% CI for the geometric mean ratio (test/reference) of <i>C</i><sub>max</sub>, AUC<sub>0-<i>t</i></sub>, and AUC<sub>0-∞</sub> were within the range of 80.00%–125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under both fasting and fed conditions. They are similar in terms of safety. This trial is registered with CTR20190366.</p>\n </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/7914586","citationCount":"0","resultStr":"{\"title\":\"Bioequivalence and Safety of Two Formulations of Tofacitinib Citrate Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions: Randomized, Open-Label, 2-Period, Single-Dose, Crossover Trials\",\"authors\":\"Yanping Liu, Yuping Ning, Yan Shi, Man Xu, Juanmin Tao, Yafen Dong, Jun Ma, Yan Qiu\",\"doi\":\"10.1155/2024/7914586\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n <p><i>Purpose</i>. To evaluate the bioequivalence of two different tofacitinib citrate tablets formulations among healthy Chinese subjects under fasting and fed conditions and to observe the safety of test preparation and reference preparation in healthy subjects. <i>Method</i>. This randomized, open-label, 2-period, crossover, bioequivalence study included 64 healthy Chinese subjects (fasting: <i>n</i> = 32, fed: <i>n</i> = 32). The subjects were assigned to receive a single 5-mg dose of the test or a reference tofacitinib citrate tablets. Blood samples were collected at predose and up to 24 hours after dosing. Area under the plasma concentration time curve from zero to the last measurable concentration (AUC<sub>0-<i>t</i></sub>), the area from time zero to infinite (AUC<sub>0-∞</sub>), and maximum plasma concentration (<i>C</i><sub>max</sub>) were used for bioequivalence assessment. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, from the time the subject receiving the test drug to the end of the last visit. <i>Results</i>. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 98.40–104.16% for AUC<sub>0-<i>t</i></sub>, 89.96–116.70% for <i>C</i><sub>max</sub>, and 98.50–104.15% for AUC<sub>0-∞</sub>. Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 93.65–101.60% for AUC<sub>0-<i>t</i></sub>, 90.06–109.15% for <i>C</i><sub>max</sub>, and 93.88–101.51% for AUC<sub>0-∞</sub>. There were no serious events. <i>Conclusion</i>. The 90% CI for the geometric mean ratio (test/reference) of <i>C</i><sub>max</sub>, AUC<sub>0-<i>t</i></sub>, and AUC<sub>0-∞</sub> were within the range of 80.00%–125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under both fasting and fed conditions. They are similar in terms of safety. This trial is registered with CTR20190366.</p>\\n </div>\",\"PeriodicalId\":15381,\"journal\":{\"name\":\"Journal of Clinical Pharmacy and Therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/7914586\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Pharmacy and Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1155/2024/7914586\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Pharmacy and Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/7914586","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Bioequivalence and Safety of Two Formulations of Tofacitinib Citrate Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions: Randomized, Open-Label, 2-Period, Single-Dose, Crossover Trials
Purpose. To evaluate the bioequivalence of two different tofacitinib citrate tablets formulations among healthy Chinese subjects under fasting and fed conditions and to observe the safety of test preparation and reference preparation in healthy subjects. Method. This randomized, open-label, 2-period, crossover, bioequivalence study included 64 healthy Chinese subjects (fasting: n = 32, fed: n = 32). The subjects were assigned to receive a single 5-mg dose of the test or a reference tofacitinib citrate tablets. Blood samples were collected at predose and up to 24 hours after dosing. Area under the plasma concentration time curve from zero to the last measurable concentration (AUC0-t), the area from time zero to infinite (AUC0-∞), and maximum plasma concentration (Cmax) were used for bioequivalence assessment. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, from the time the subject receiving the test drug to the end of the last visit. Results. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 98.40–104.16% for AUC0-t, 89.96–116.70% for Cmax, and 98.50–104.15% for AUC0-∞. Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 93.65–101.60% for AUC0-t, 90.06–109.15% for Cmax, and 93.88–101.51% for AUC0-∞. There were no serious events. Conclusion. The 90% CI for the geometric mean ratio (test/reference) of Cmax, AUC0-t, and AUC0-∞ were within the range of 80.00%–125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under both fasting and fed conditions. They are similar in terms of safety. This trial is registered with CTR20190366.
期刊介绍:
The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including:
Rational therapeutics
Evidence-based practice
Safety, cost-effectiveness and clinical efficacy of drugs
Drug interactions
Clinical impact of drug formulations
Pharmacogenetics
Personalised, stratified and translational medicine
Clinical pharmacokinetics.