{"title":"中国健康人空腹和餐后条件下氯培司汀的药代动力学、生物等效性和安全性。","authors":"Hong-Yu Luo, Hui-Zhi Long, Zi-Wei Zhou, Shuo-Guo Xu, Feng-Jiao Li, Yan Cheng, Dan-Dan Wen, Ping Deng, Li-Chen Gao","doi":"10.1007/s40268-022-00406-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.</p><p><strong>Objective: </strong>The purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.</p><p><strong>Methods: </strong>A single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC<sub>0-72h</sub>), under the plasma concentration-time curve from zero to infinity (AUC<sub>0-∞</sub>) and the maximal plasma concentration (C<sub>max</sub>). The equivalence standard range (80.0-125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs).</p><p><strong>Results: </strong>A total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the C<sub>max</sub>, AUC<sub>0-72h</sub> and AUC<sub>0-∞</sub> were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the C<sub>max</sub>, AUC<sub>0-72h</sub> and AUC<sub>0-∞</sub> were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0-125.0%). The C<sub>max</sub> and AUC<sub>0-72h</sub> values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial.</p><p><strong>Conclusions: </strong>The T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/43/ac/40268_2022_Article_406.PMC9651896.pdf","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics, Bioequivalence and Safety of Cloperastine in Chinese Healthy Subjects Under Fasting and Postprandial Conditions.\",\"authors\":\"Hong-Yu Luo, Hui-Zhi Long, Zi-Wei Zhou, Shuo-Guo Xu, Feng-Jiao Li, Yan Cheng, Dan-Dan Wen, Ping Deng, Li-Chen Gao\",\"doi\":\"10.1007/s40268-022-00406-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.</p><p><strong>Objective: </strong>The purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.</p><p><strong>Methods: </strong>A single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC<sub>0-72h</sub>), under the plasma concentration-time curve from zero to infinity (AUC<sub>0-∞</sub>) and the maximal plasma concentration (C<sub>max</sub>). The equivalence standard range (80.0-125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs).</p><p><strong>Results: </strong>A total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the C<sub>max</sub>, AUC<sub>0-72h</sub> and AUC<sub>0-∞</sub> were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the C<sub>max</sub>, AUC<sub>0-72h</sub> and AUC<sub>0-∞</sub> were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0-125.0%). The C<sub>max</sub> and AUC<sub>0-72h</sub> values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial.</p><p><strong>Conclusions: </strong>The T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.</p>\",\"PeriodicalId\":49258,\"journal\":{\"name\":\"Drugs in Research & Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/43/ac/40268_2022_Article_406.PMC9651896.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drugs in Research & Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40268-022-00406-2\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/11/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drugs in Research & Development","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40268-022-00406-2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/11/11 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Pharmacokinetics, Bioequivalence and Safety of Cloperastine in Chinese Healthy Subjects Under Fasting and Postprandial Conditions.
Background: Cloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.
Objective: The purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.
Methods: A single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC0-72h), under the plasma concentration-time curve from zero to infinity (AUC0-∞) and the maximal plasma concentration (Cmax). The equivalence standard range (80.0-125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs).
Results: A total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the Cmax, AUC0-72h and AUC0-∞ were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the Cmax, AUC0-72h and AUC0-∞ were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0-125.0%). The Cmax and AUC0-72h values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial.
Conclusions: The T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.
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.
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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.