A limited sampling approach in bioequivalence studies: application to longhalf-life drugs and replicate design studies

Objectives: The objectives of this study was to develop a limited sampling model (LSM) to predict the area under the curve (AUC) and the maximum plasm a concentration (C-max) for the assessment of bioequivalence studies. Metho ds: Two drugs (A and B) were selected for this purpose. Drug A was chosen t o test bioequivalence of two formulations with a long half-life (> 35 hours ), whereas drug B was chosen to test the bioequivalence of two formulations (half-life = 12 hrs) with a replicate design study. The LSM for both drugs was developed using 5 blood samples each from 15 healthy subjects. The rel ationship between plasma concentration (independent variable) at selected t ime points with the AUC or C-max (dependent variable) was evaluated by mult iple linear regression analysis, The multiple linear regression which gave the best correlation coefficient (r) for 5 sampling time vs AUC or C-max wa s chosen as the LSM. The predicted AUC and C-max from the LSM were then use d to assess bioequivalence of two different formulations of each drug follo wing a single oral dose. Results: The model provided good estimates of both AUC and C-max for both drugs. The 90% confidence intervals an log-transfor med observed and predicted AUC and C-max were comparable for both drugs. Co nclusions: The method described here may be used to estimate AUC and C-max for bioequivalence studies for drugs with long half-lives or for highly var iable drugs which may require replicate design studies without detailed blo od sampling.