To establish bioequivalence of 50mg Metoprolol Succinate extended release tablets in normal, healthy, adult, human subject under fasting condition
Oral drug delivery is the most preferred route for the various drug molecules among all other routes of drug delivery, because ease of administration which lead to better patient compliance. So, oral extended release drug delivery system becomes a very promising approach for those drugs that are given orally but having the shorter half-life and high dosing frequency. Extended release Extended-release systems allow for the drug to be released over prolonged time periods. By extending the release profile of a drug, the frequency of dosing can be reduced. The study was an open label, balanced, randomized, three-treatment, three-period, three-sequence, single oral dose, crossover, bioequivalence study in normal healthy adult human subjects under fasting condition, with a screening period of 28 days prior to IMP administration in Period-I. In each study period, 27 blood samples, including one pre-dose blood sample, were collected from each subject except for the discontinued / withdrawn subjects to analyze the pharmacokinetic profile of the two test products (T1 and T2) as well as the reference product. The pharmacokinetic parameters were calculated from the plasma concentration vs. time profile by non-compartmental model using Phoenix® WinNonlin® Version 6.4 (Certara L.P.) for Metoprolol. Out of 18 subjects enrolled, data of 13 subjects were analyzed. Mean Cmax is 31.634 ± 22.6007 ng/mL, 31.241 ± 20.6090 ng/mL and 31.773 ± 23.1819 ng/mL, mean AUCo-t is722.992 ± 584.3793 ng hr/mL, 658.192 ± 492.3416 ng hr/mL and 706.219 ± 546.5064 ng hr/mL, mean AUC0-inf is 751.204 ± 631.9623 ng hr/mL, 676.939 ± 519.1306 ng hr/mL and729.505 ± 578.1691 ng hr/mL for test product (T1), test product (T2) and reference product (R).Test Products (T1 and T2) when compared with the Reference Product-R meets the bioequivalence criteria with respect to Cmax, AUC0-t and AUC0-∞ for Metoprolol under fasting condition as per criteria set in the protocol.
2. Jantzen GM and Robinson JR. Sustained and Controlled-Release Drug Delivery systems. Modern Pharmaceutics., 1995; 121(4): 501-502.
3. Wani MS. Controlled Release System A Review; Pharmaceutical Reviews., 2008; 6(1):41-46.
4. Hayashi T. Formulation, study and drug release mechanism of a new Theophylline sustained release preparation, Int. J Pharm., 2005; 304: 91-101.
5. Venkatraman S, Davar N and Chester A. An overview of controlled release systems: Edited by Donald L Wise, New York, Marcel Dekker Inc. Handbook of Pharmaceutical controlled release Technology., 2000; 431-465.
6. Kulkarni JS., Pawar AP., Shedbakar VP., Biopharmaceutics and Pharmacokinetics, CBS Publishers and Distributors, New Delhi, 2006, page No. 249-262.
7. U.S. Department of Health and Human Services, Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products — General Considerations, Food and Drug Administration Center for Drug Evaluation and Research (CDER), March 2003 BP, Revision 1.
8. Saudi Food and Drug Authority, Bioequivalence Requirements guidelines, Kingdom of Saudi Arabia, Drug Sector, Draft May 2005.
9. Marzo A, ―Clinical pharmacokinetic registration file for NDA and ANDA procedures.‖ Pharmacol Res. 1997, 36(6):425-450.
10. Bahar MA, Kamp J, Borgsteede SD, Hak E, Wilffert B: The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine. Br J Clin Pharmacol. 2018 Dec, page No. 2704-2715.
11. Frishman W., Cheng-Lai A. and Nawarskas J. (2005). Current cardiovascular drugs (4th ed.). Current medicine LLC.
12. Tsigos C, Kyrou I, Kassi E, Chrousos GP. Stress, Endocrine Physiology and Pathophysiology. Endotext. MDText.com, Inc.; 2000.
13. Bahar MA, Kamp J, Borgsteede SD, Hak E, Wilffert B: The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine. Br J Clin Pharmacol. 2018 Dec, page No. 2704-2715)
14. University of Illinois-Chicago - Drug Information Group. Metoprolol Tartrate vs. Metoprolol Succinate [Internet]. 2016 [cited 2018 Feb 27].
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).