Assessment of polymorphic metabolite data in bioavailability/bioequivalence studies – considerations and challenges

Main Article Content

Nuggehally R Srinivas


Bioavailability (BA)/ bioequivalence (BE) studies are the cornerstone for the approval of generic drugs. While BA/BE assessment involving the pharmacokinetic data of the parent compound has been routinely performed, the introduction of the assessment of metabolite(s) data, alone or in addition to parent compound, has also emerged. In this context, the assessment of BA/BE of metabolite(s) may pose additional complexities and challenges, if the metabolic pathway is under
the influence of a polymorphic enzyme. This communication provides brief perspectives on the challenges and study design considerations for the assessment of polymorphic metabolite in BA/BE studies.


Download data is not yet available.

Article Details

How to Cite
Srinivas, N. R. (2014). Assessment of polymorphic metabolite data in bioavailability/bioequivalence studies – considerations and challenges. Asian Journal of Pharmaceutics (AJP), 5(3).


Colburn WA, Keefe DL. Bioavailability and bioequivalence: Average,

population and/or individual. J Clin Pharmacol 2000;40:559-60.

Yacobi A, Masson E, Moros D, Ganes D, Lapointe C, Abolfathi Z, et al.

Who needs individual bioequivalence studies for narrow therapeutic

index drugs? A case for warfarin. J Clin Pharmacol 2000;40:826-35.

Bialer M, Midha KK. Generic products of antiepileptic drugs: A

perspective on bioequivalence and interchangeability. Epilepsia


Zariffa NM, Patterson SD. Population and individual bioequivalence:

lessons from real data and simulation studies. J Clin Pharmacol


Zariffa NM, Patterson SD, Boyle D, Hyneck M. Case studies, practical

issues and observations on population and individual bioequivalence.

Stat Med 2000;19:2811-20.

Karalis V, Symillides M, Macheras P. Novel methods to assess

bioequivalence. Expert Opin Drug Metab Toxicol 2011;7:79-88.

Srinivas NR. Considerations for metabolite pharmacokinetic data in

bioavailability/bioequivalence assessments - Overview of the recent

trends. Arzneimittelforschng 2009;59:155-65.

Tomalik-Scharte D, Lazar A, Fuhr U, Kirchheiner J. The clinical

role of genetic polymorphisms in drug-metabolizing enzymes.

Pharmacogenomics J 2008;8:4-15.

Bijl MJ, Luijendijk HJ, van den Berg JF, Visser LE, van Schaik RH,

Hofman A, et al. Association between the CYP2D6*4 polymorphism and

depression or anxiety in the elderly. Pharmacogenomics 2009;10:541-7.

Ginsberg G, Smolenski S, Neafsey P, Hattis D, Walker K, Guyton KZ, et al.The influence of genetic polymorphisms on population variability in

six xenobiotic-metabolizing enzymes. J Toxicol Environ Health B Crit

Rev 2009;12:307-33.

Johansson I, Ingelman-Sundberg M. Genetic polymorphism and

toxicology-with emphasis on cytochrome p450. Toxicol Sci 2011;120:1-13.

Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450

enzymes and its clinical impact. Drug Metab Rev 2009;41:89-295.

Solans A, Izquierdo I, Donado E, Antonijoan R, Peña J, Nadal T, et al.

Pharmacokinetic and safety profile of rupatadine when coadministered

with azithromycin at steady-state levels: A randomized, open-label,

two-way, crossover, Phase I study. Clin Ther 2008;30:1639-50.

Katiyar S, Prakash S. Systematic review: Pharmacological profile,

efficacy and safety of rupatadine in allergic rhinitis. Primary Care Resp

J 2009;18:57-68.

Frick GS, Blum RA, Kovacs SJ, Lone. Prevalence of the slow metabolizer

(SM) phenotype and single dose pharmacokinetics (PK) of desloratadine

(DCL) in a population of healthy adults. Clin Pharmacol Ther 2004;75:9.

Available from: [Last

accessed on 2011 Jul 20].

Prenner B, Kim K, Gupta S, Khalilieh S, Kantesaria B, Manitpisitkul P, et al.

Adult and pediatric poor metabolisers of desloratadine: An assessment

of pharmacokinetics and safety. Expert Opin Drug Saf 2006;5:211-23.

Srinivas NR. Unsuspected polymorphic metabolism of rupatadine via its primary metabolite, desloratadine. Prim Care Respir J 2009;18:118-9.