A LIMITED SAMPLING APPROACH IN BIOEQUIVALENCE STUDIES

A limited sampling model (LSM) has been developed for an antidepressan t immediate-release product (Drug A) and an antiepileptic controlled r elease product (Drug B) to predict the area under the curve (AUC) and the maximum plasma concentration (C-max) and to compare the bioequival ence of two formulations of each drug using predicted versus observed AUC and C-max after a single oral dose. The LSM for drug A was develop ed using data from 10 healthy people. The correlation between plasma c oncentration (independent variable) at selected time points with the A UC or C-max (dependent variable) was evaluated by simple regression an alysis. The linear regression that gave the best correlation coefficie nt (r) for a single sampling time versus AUC or C-max was chosen as th e LSM. The model provided good estimates of AUC and C-max for drug A. The 90% confidence interval on log transformed observed and predicted AUC and C-max were as follows: AUC observed = 100% to 118%, AUC predic ted = 101% to 117%, C-max observed = 99% to 125%, and C-max predicted = 100% to 131%. The LSM for drug B was developed using a similar appro ach to drug A. The 90% confidence interval on log transformed observed and predicted AUC and C-max were: AUC observed = 99% to 110%, AUC pre dicted = 99% to 118%, C-max observed = 107% to 120%, and C-max predict ed = 99% to 111%. Although the predicted C-max did not meet the 90% co nfidence interval for drug A, the method described here may be used to estimate AUC and C-max for a drug in bioequivalence studies without d etailed blood sampling. More research is needed in this direction.