Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects
The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, ran...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383515001446 |
| _version_ | 1828771742242308096 |
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| author | Fang Tang Rui Zhou Zeneng Cheng Guoping Yang Aiqiao Chen Zhi Liu Hongyi Tan Shuang Yang Sanwang Li Lingli Mu Peng Yu |
| author_facet | Fang Tang Rui Zhou Zeneng Cheng Guoping Yang Aiqiao Chen Zhi Liu Hongyi Tan Shuang Yang Sanwang Li Lingli Mu Peng Yu |
| author_sort | Fang Tang |
| collection | DOAJ |
| description | The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and Cmax of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and Cmax of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of Cmax, AUC0–t and AUC0–∞ of agomelatine (104.42–139.86, 101.33–123.83 and 97.90–117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55–123.03, 101.95–109.10 and 101.72–108.70) and 7-desmethyl-agomelatine (104.50–125.23, 102.36–111.50 and 101.62–110.64) were within the FDA bioequivalence definition intervals (0.80–1.25 for AUC and 0.75–1.33 for Cmax). The RSABE approach was successful in evaluating the bioequivalence of these two formulations. |
| first_indexed | 2024-12-11T14:30:56Z |
| format | Article |
| id | doaj.art-4a9a781000424794bd7bdcfb504103b4 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 2211-3843 |
| language | English |
| last_indexed | 2024-12-11T14:30:56Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-4a9a781000424794bd7bdcfb504103b42022-12-22T01:02:25ZengElsevierActa Pharmaceutica Sinica B2211-38352211-38432016-01-0161717810.1016/j.apsb.2015.10.003Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjectsFang Tang0Rui Zhou1Zeneng Cheng2Guoping Yang3Aiqiao Chen4Zhi Liu5Hongyi Tan6Shuang Yang7Sanwang Li8Lingli Mu9Peng Yu10School of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaThe Third Xiangya Hospital, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaHunan Tiger-Xiangya R&D Company Ltd., Changsha 410013, ChinaThe Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Third Xiangya Hospital, Central South University, Changsha 410013, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaMedical College, Hunan Normal University, Changsha 410006, ChinaSchool of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaThe aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and Cmax of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and Cmax of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of Cmax, AUC0–t and AUC0–∞ of agomelatine (104.42–139.86, 101.33–123.83 and 97.90–117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55–123.03, 101.95–109.10 and 101.72–108.70) and 7-desmethyl-agomelatine (104.50–125.23, 102.36–111.50 and 101.62–110.64) were within the FDA bioequivalence definition intervals (0.80–1.25 for AUC and 0.75–1.33 for Cmax). The RSABE approach was successful in evaluating the bioequivalence of these two formulations.http://www.sciencedirect.com/science/article/pii/S2211383515001446Reference-scaled average bioequivalenceAgomelatine3-Hydroxy-agomelatine7-Desmethyl-agomelatineChinese subjectsHigh variabilityGeneric drug |
| spellingShingle | Fang Tang Rui Zhou Zeneng Cheng Guoping Yang Aiqiao Chen Zhi Liu Hongyi Tan Shuang Yang Sanwang Li Lingli Mu Peng Yu Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects Acta Pharmaceutica Sinica B Reference-scaled average bioequivalence Agomelatine 3-Hydroxy-agomelatine 7-Desmethyl-agomelatine Chinese subjects High variability Generic drug |
| title | Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects |
| title_full | Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects |
| title_fullStr | Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects |
| title_full_unstemmed | Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects |
| title_short | Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects |
| title_sort | implementation of a reference scaled average bioequivalence approach for highly variable generic drug products of agomelatine in chinese subjects |
| topic | Reference-scaled average bioequivalence Agomelatine 3-Hydroxy-agomelatine 7-Desmethyl-agomelatine Chinese subjects High variability Generic drug |
| url | http://www.sciencedirect.com/science/article/pii/S2211383515001446 |
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