REFERENCE-SCALED AVERAGE BIOEQUIVALENCE STUDY OF PAROXETINE UNDER FED CONDITIONS: VALIDATION OF SAMPLE SIZE ESTIMATION BY BOOTSTRAPPING TECHNIQUE
Objective: New technique was adopted and validated to estimate pivotal sample size from the pilot study data and to establish bioequivalence (BE) of highly variable drugs (HVD), paroxetine, a novel controlled release (CR) matrix tablets utilized ghatti Gum as a rate controlling membrane, in human subject under fed conditions by reference scale design.
Methods: Bootstrapping technique was adopted to calculate the pivotal sample size from pilot study data for HVD paroxetine. The reliability and validation of the method were tested in a semi replicate three sequence (RRT, RTR, and TRR where T stand for test drug and R stand for reference drug) cross-over BE study in 24 healthy subjects under fed conditions.
Results: The ratio of the pharmacokinetic (PK) metric obtained from the bootstrapping technique after log transformation was 1.04 for Cmax, 1.23 for AUCT, and 1.21 for AUCI with corresponding power of the study which was greater than 80% from pilot study data simulation. The ratio of the PK metric obtained from the reference scaling design in the present study was 1.00 for Cmax, 1.21 for AUCT, and 1.17 for AUCI. The upper limit of the Cmax, AUCT, and AUCI at 95% confidence limit was −0.143, −0.136, and −0.17, respectively.
Conclusion: The test paroxetine CR formulation was bioequivalent with reference drug under fed conditions. The technique used for estimation of the sample size in the pivotal study was found reliable, and bootstrapping technique plays an important role in calculating sample size where intrasubject variability was immaterial.
2. Kaye CM, Haddock RE, Langley PF, Mellows G, Tasker TC, Zussman BD, et al. A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr Scand Suppl 1989;350:60-75.
3. Robert MN, Samuel TG, Bryman EW. Paroxetine-the antidepressant from hell? Probably not, but caution required. Psychopharmacol Bull 2016;46:77-104.
4. Benbow SJ, Gill G. Paroxetine hepatotoxicity. Br Med J 1997;314:1387-94.
5. Caccia S. Metabolism of the newer antidepressants. Clin Pharmacokinet 1998;34:281-302.
6. Goldberg RJ. Antidepressant use in the elderly. Drugs Aging 1995;11:119-31.
7. Boyer WF, Feighner JP. An overview of paroxetine. J Clin Psychiatry 1992;53:3-6.
8. Eap CB, Baumann P. Analytical methods for the quantitative determination of selective serotonin reuptake inhibitors for therapeutic drug monitoring purposes in patients. J Chromatogr B 1996;686:51-63.
9. Dechant KL, Clissold SP. Paroxetine: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs 1991;41:225-53.
10. Geretsegger G, Bohmer F, Ludwing M. Paroxetine in the elderly depressed patients: Randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects. Int Clin Psychopharmacol 1994;9:25-9.
11. Gunasekara NS, Noble S, Benfield P. Paroxetine: An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders. Drugs 1998;55:85-120.
12. Nemeroff CB. Paroxetine: An overview of the efficacy and safety of a new selective serotonin reuptake inhibitor in the treatment of depression. J Clin Psychopharmacol 1993;13:10-7.
13. Guidance for Industry, SUPAC-IR/MR: Immediate Release and Modified Release Solid Oral Dosage Forms U S Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) 1997, Manufacturing Equipment Addendum, (Revision 1); 1999.
14. Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products-General Gonsiderations (Revision 1). U S Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); 2008.
15. The European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit, International Conference on Harmonisation. Guideline for Good Clinical Practice [EMEAWeb site]. Available from: http://www.emea.eu.int. [Last accessed 2007 Mar 26].
16. European Medical Agency Guideline on the Investigation of Bioequivalence CPMP/EWP/QWP/1401/98 Rev. 1, London; 2010.
17. Reddy PS, Bose PS, Saritha D, Sruthi V. Formulation and evaluation of colon targeted matrix tablet using natural tree gums. Int J Pharm Pharm Sci 2018;10:92-7.
18. Zhu Z, Neirinck L. High-performance liquid chromatography-mass spectrometry method for the determination of paroxetine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2002;780:295-300.
19. Maurer HH, Bickeboeller-Friedrich J. Screening procedure for detection of antidepressants of the selective serotonin reuptake inhibitor type and their metabolites in urine as part of a modified systematic toxicological analysis procedure using gas chromatography-mass spectrometry. J Anal Toxicol 2000;24:340-7.
20. Maralikova B, WeinmannW. Confirmatory analysis for drugs of abuse in plasma and urine by high-performance liquid chromatography-tandem mass spectrometry with respect to criteria for compound identification. J Chromatogr B 2004;811:21-30.
21. Naidong W, Eerkes A. Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the analysis of paroxetine in human plasma. Biomed Chromatogr 2004;18:28-36.
22. Eap CB, Bouchoux G, Amey M, Cochard N, Savary L, Baumann P. Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline and their metabolites by gas chromatography-mass spectrometry. J Chromatogr Sci 1998;36:365-71.
23. Juan H, Zhiling Z, Huande L. Simultaneous determination of fluoxetine, citalopram, paroxetine, venlafaxine in plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). J Chromatogr B Analyt Technol Biomed Life Sci 2005;820:33-9.
24. Erk N, Biryol I. Voltammetric and HPLC techniques for the determination of paroxetine hydrochloride. J Pharmazie 2003;58:699-704.
25. Duverneul C, de la Grandmaison GL, de Mazancourt P, Alvarez JC. A high-performance liquid chromatography method with photodiode-array UV detection for therapeutic drug monitoring of the nontricyclic antidepressant drugs. Ther Drug Monit 2005;25:565-73.
26. Lopez-Calull C, Dominguez N. Determination of paroxetine in plasma by high-performance liquid chromatography for bioequivalence studies. J Chromatogr B Biomed Sci Appl 1999;724:393-8.
27. Bonato PS, Lanchote VL. A rapid procedure for the purification of biological samples to be analyzed by high-performance liquid chromatography. J Liq Chromatogr 1993;16:2299-308.
28. Martin AB, Dierdorf HD, Barry DZ, Peter EC. Determination of paroxetine in human plasma, using high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987;419:438-44.
29. Reddy GS, Reddy SL, Reddy SK. Development and validation of a stability indicating liquid chromatographic method for the simultaneous estimation of paroxetine and clonazepam in bulk and its pharmaceutical formulations. Int J Pharm Pharm Sci 2014;10:397-402.
30. Stephen JW, Michael JC. The use of bootstrap methods for estimating sample size and analyzing health-related quality of life outcomes. Stat Med 2005;24:1075-102.
31. Yuan KH, Hayashi K. Bootstrap approach to inference and power analysis based on three test statistics for covariance structure models. Br J Math Stat Psychol 2003;56:93-110.
32. Chow SC, Shao J, Wang H. Sample Size Calculation in Clinical Research. New York: Marcel Dekker Inc.; 2003.
33. Peng X, Peng G, Gonzales C. Power Analysis and Sample Size Estimation using Bootstrap, Paper sp05. Indianapolis, IN: Eli Lilly and Company.
34. Thompson D. Bootstrap Power Analysis using SAS®+ Paper SA-13. Chicago, IL: Thompson Research Consulting LLC.
35. Shumaker RC. Pkcalc: A basic interactive computer program for statistical and pharmacokinetic analysis of data. Drug Metab Rev 1986;17:331-48.
36. Tothfalusi L, Endrenyi L. Limits for the scaled average bioequivalence of highly variable drugs and drug products. Pharm Res 2010;20:382-89.
37. Kamal KM, Maureen JR, John WH. Individual and average bioequivalence of highly variable drugs and drug products. J Pharm Sci 2000;86:1193-97.
38. Chow SC, Liu JP. Design and Analysis of Bioavailability and Bioequivalence Studies. New York: Marcel Dekker Inc.; 1992.
39. Baek I, Lee BY, Kang W, Kwon KI. Comparison of average, scaled average, and population bioequivalence methods for assessment of highly variable drugs: An experience with doxifluridine in beagle dogs. Eur J Pharm Sci 2010;39:175-80.
40. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm 1987;15:657-80.
41. Tothfalusi L, Endrenyf L, Arieta AG. Evaluation of bioequivalence for highly variable drugs with scaled average bioequivalence. Clin Pharmacokinet 2009;48:725-43.
42. Sam HH, Makhlouf F, Donald JS, Hyslop T, Davit B, Conner D, et al. Evaluation of a scaling approach for the bioequivalence of highly variable drugs. AAPS J 2008;10:450-4.
43. Davit BM, Conner DP, Fabian-Fritsch B, Haidar SH, Jiang X, Patel DT, et al. Highly variable drugs: Observations from bioequivalence data submitted to the FDA for new generic drug applications. AAPS J 2008;10:148-56.
44. Haidar SH, Davit B, Chen ML, Conner D, Lee LM, Li QH, et al. Bioequivalence approaches for highly variable drugs and drug products. Pharm Res 2008;25:1237-41.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.