Esra DEMİRTÜRK*,o, Levent ÖNER*

*Hacettepe University, Faculty of Pharmacy, Department of Pharmacetical Thecnology, 06100, Ankara, TURKEY.
oCorresponding author

Summary:
Drugs and drug products which exhibit intra-subject variabilities of more than 30% are classified as highly variable. In bioequivalance studies the effects of physiological factors of subjects, physico-chemical and pharmacokinetic properties of the drug substance, formulation variabilities of the final product on bioavailability are tried to be lowered as much as possible. Multiple- dose, replicate and group sequential (add-on subject design) study designs are recommended while studying the highly variable drugs. In some cases where the acceptance criterion in bioequivalence studies is used the problems in evaluation of bioequivalence may not be solved with the above study designs, statistical evaluations such as reducing the level of the confidence interval and widening the bioequivalence interval as well as multiple dose studies and add-on subject designs can be used providing that they do not undermine the safety of the drug.