Zhao-Xin Wu, Chen-Jing Wang, Ping Shi, Yan-Ping Liu, Ting Li, Fei-Fei Sun, Yao Fu, Xiao-Meng Gao, Ya-Ping Ma, Yu Cao
{"title":"醋酸阿比特龙片在中国健康志愿者体内的药代动力学和生物等效性:一项开放、随机、单剂量、三期、三序列的交叉研究","authors":"Zhao-Xin Wu, Chen-Jing Wang, Ping Shi, Yan-Ping Liu, Ting Li, Fei-Fei Sun, Yao Fu, Xiao-Meng Gao, Ya-Ping Ma, Yu Cao","doi":"10.1007/s40268-023-00418-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Abiraterone acetate tablet is an inhibitor of androgen synthesis, primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioequivalence and pharmacokinetics of the reference and test formulations of abiraterone acetate tablets in healthy Chinese volunteers.</p><p><strong>Methods: </strong>A single-center, open, single-dose, randomized, three-period, three-sequence, semi-repeat (only repeated reference formulations), and reference formulation-corrected fasting reference-scaled average bioequivalence test was conducted in 36 healthy volunteers included in this study. Volunteers were randomly assigned to one of three groups in a 1:1:1 ratio. There was a minimum 7-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of abiraterone acetate tablets was determined by liquid chromatography-tandem mass spectrometry, and adverse events were recorded.</p><p><strong>Results: </strong>Under fasting conditions, the maximum plasma concentration (C<sub>max</sub>) was 27.02 ± 14.21 ng/mL, area under the concentration-time curve from time zero to time t (AUC<sub>t</sub>) was 125.30 ± 82.41 h·ng/mL, and AUC from time zero to infinity (AUC<sub>∞</sub>) was 133.70 ± 83.99 h·ng/mL. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of AUC<sub>t</sub> and AUC<sub>∞</sub> were in the range of 0.8000-1.2500, and the coefficient of variation (CV<sub>WR</sub>) of C<sub>max</sub> was more than 30%. The Critbound result was - 0.0522, and the GMR was between 0.8000 and 1.2500.</p><p><strong>Conclusion: </strong>Both test and reference formulations of abiraterone acetate tablets were bioequivalent in healthy Chinese subjects under fasting conditions.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT04863105, registered 26 April 2021-retrospectively registered ( https://register.</p><p><strong>Clinicaltrials: </strong>gov/prs/app/action/SelectProtocol?sid=S000ARAA&selectaction=Edit&uid=U00050YQ&ts=2&cx=-vbtjri.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/21/40268_2023_Article_418.PMC10293147.pdf","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics and Bioequivalence of Abiraterone Acetate Tablets in Healthy Chinese Volunteers: An Open, Randomized, Single-Dose, Three-Period, Three-Sequence Crossover Study.\",\"authors\":\"Zhao-Xin Wu, Chen-Jing Wang, Ping Shi, Yan-Ping Liu, Ting Li, Fei-Fei Sun, Yao Fu, Xiao-Meng Gao, Ya-Ping Ma, Yu Cao\",\"doi\":\"10.1007/s40268-023-00418-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Abiraterone acetate tablet is an inhibitor of androgen synthesis, primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioequivalence and pharmacokinetics of the reference and test formulations of abiraterone acetate tablets in healthy Chinese volunteers.</p><p><strong>Methods: </strong>A single-center, open, single-dose, randomized, three-period, three-sequence, semi-repeat (only repeated reference formulations), and reference formulation-corrected fasting reference-scaled average bioequivalence test was conducted in 36 healthy volunteers included in this study. Volunteers were randomly assigned to one of three groups in a 1:1:1 ratio. There was a minimum 7-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of abiraterone acetate tablets was determined by liquid chromatography-tandem mass spectrometry, and adverse events were recorded.</p><p><strong>Results: </strong>Under fasting conditions, the maximum plasma concentration (C<sub>max</sub>) was 27.02 ± 14.21 ng/mL, area under the concentration-time curve from time zero to time t (AUC<sub>t</sub>) was 125.30 ± 82.41 h·ng/mL, and AUC from time zero to infinity (AUC<sub>∞</sub>) was 133.70 ± 83.99 h·ng/mL. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of AUC<sub>t</sub> and AUC<sub>∞</sub> were in the range of 0.8000-1.2500, and the coefficient of variation (CV<sub>WR</sub>) of C<sub>max</sub> was more than 30%. 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Pharmacokinetics and Bioequivalence of Abiraterone Acetate Tablets in Healthy Chinese Volunteers: An Open, Randomized, Single-Dose, Three-Period, Three-Sequence Crossover Study.
Background and objective: Abiraterone acetate tablet is an inhibitor of androgen synthesis, primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioequivalence and pharmacokinetics of the reference and test formulations of abiraterone acetate tablets in healthy Chinese volunteers.
Methods: A single-center, open, single-dose, randomized, three-period, three-sequence, semi-repeat (only repeated reference formulations), and reference formulation-corrected fasting reference-scaled average bioequivalence test was conducted in 36 healthy volunteers included in this study. Volunteers were randomly assigned to one of three groups in a 1:1:1 ratio. There was a minimum 7-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of abiraterone acetate tablets was determined by liquid chromatography-tandem mass spectrometry, and adverse events were recorded.
Results: Under fasting conditions, the maximum plasma concentration (Cmax) was 27.02 ± 14.21 ng/mL, area under the concentration-time curve from time zero to time t (AUCt) was 125.30 ± 82.41 h·ng/mL, and AUC from time zero to infinity (AUC∞) was 133.70 ± 83.99 h·ng/mL. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of AUCt and AUC∞ were in the range of 0.8000-1.2500, and the coefficient of variation (CVWR) of Cmax was more than 30%. The Critbound result was - 0.0522, and the GMR was between 0.8000 and 1.2500.
Conclusion: Both test and reference formulations of abiraterone acetate tablets were bioequivalent in healthy Chinese subjects under fasting conditions.
期刊介绍：
Drugs in R&D is an international, peer reviewed, open access, online only journal, and provides timely information from all phases of drug research and development that will inform clinical practice. Healthcare decision makers are thus provided with knowledge about the developing place of a drug in therapy.
The Journal includes:
Clinical research on new and established drugs;
Preclinical research of direct relevance to clinical drug development;
Short communications and case study reports that meet the above criteria will also be considered;
Reviews may also be considered.
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