{"title":"阿哌沙班片在中国健康受试者空腹和喂养条件下的药代动力学、安全性和生物等效性","authors":"Hong-Yu Luo, Zhen-Jiang Yao, Hui-Zhi Long, Zi-Wei Zhou, Shuo-Guo Xu, Feng-Jiao Li, Yan Cheng, Dan-Dan Wen, Ping Deng, Yue-Qing Guan, Li-Chen Gao","doi":"10.5414/CP204299","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions.</p><p><strong>Materials and methods: </strong>A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC<sub>0-t</sub> and AUC<sub>0-∞</sub>) and the maximal plasma concentration (C<sub>max</sub>). Safety was assessed mainly from the occurrence of adverse events (AEs).</p><p><strong>Results: </strong>A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC<sub>0-t</sub> were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC<sub>0-∞</sub> were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for C<sub>max</sub> were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and C<sub>max</sub> ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs).</p><p><strong>Conclusion: </strong>The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":"61 3","pages":"129-138"},"PeriodicalIF":0.9000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics, safety, and bioequivalence of apixaban tablets in healthy Chinese subjects under fasting and fed conditions.\",\"authors\":\"Hong-Yu Luo, Zhen-Jiang Yao, Hui-Zhi Long, Zi-Wei Zhou, Shuo-Guo Xu, Feng-Jiao Li, Yan Cheng, Dan-Dan Wen, Ping Deng, Yue-Qing Guan, Li-Chen Gao\",\"doi\":\"10.5414/CP204299\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions.</p><p><strong>Materials and methods: </strong>A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC<sub>0-t</sub> and AUC<sub>0-∞</sub>) and the maximal plasma concentration (C<sub>max</sub>). Safety was assessed mainly from the occurrence of adverse events (AEs).</p><p><strong>Results: </strong>A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC<sub>0-t</sub> were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC<sub>0-∞</sub> were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for C<sub>max</sub> were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and C<sub>max</sub> ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs).</p><p><strong>Conclusion: </strong>The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.</p>\",\"PeriodicalId\":13963,\"journal\":{\"name\":\"International journal of clinical pharmacology and therapeutics\",\"volume\":\"61 3\",\"pages\":\"129-138\"},\"PeriodicalIF\":0.9000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of clinical pharmacology and therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.5414/CP204299\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of clinical pharmacology and therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5414/CP204299","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Pharmacokinetics, safety, and bioequivalence of apixaban tablets in healthy Chinese subjects under fasting and fed conditions.
Objective: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions.
Materials and methods: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs).
Results: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs).
Conclusion: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.
期刊介绍：
The International Journal of Clinical Pharmacology and Therapeutics appears monthly and publishes manuscripts containing original material with emphasis on the following topics: Clinical trials, Pharmacoepidemiology - Pharmacovigilance, Pharmacodynamics, Drug disposition and Pharmacokinetics, Quality assurance, Pharmacogenetics, Biotechnological drugs such as cytokines and recombinant antibiotics. Case reports on adverse reactions are also of interest.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
