Impact of truncated area under the curve on failed bioequivalence studies: a computer simulation analysis.
The common measures used in a bioequivalence study are area under the curve (AUC) and the maximum plasma concentration. Estimation of AUC requires frequent blood samples. For long half-life drugs, sampling for long periods of time may become cumbersome. To resolve this issue some investigators have suggested the use of truncated AUC in bioequivalence studies for long half-life drugs. The suggested length of time for the truncated AUC is 72 hours. Many studies have been conducted to show that truncated AUC till 72 hours is a suitable approach. However, the suitability of truncated AUC for failed bioequivalence study has not been demonstrated. This report of simulated plasma concentration versus time data evaluates the suitability of truncated AUC for failed bioequivalence study of two hypothetical drugs. The results of the study indicate that the truncated approach for the estimation of the AUC for long half-life drugs in bioequivalence studies may be useful but it also increases the probability of accepting drugs as being bioequivalent when they are not.
Division of Clinical Trial Design and Analysis, Office of Therapeutic Research and Review, Clinical Pharmacology and Toxicology Branch, Food & Drug Administration, Rockville, MD 20852, USA. mahmoodi@cber.fda.gov
Iftekhar
I
Mahmood
D019540:Area Under Curve; D003198:Computer Simulation; D016001:Confidence Intervals; D006207:Half-Life; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000097:blood; D013810:Therapeutic Equivalency; D013997:Time Factors
D004364:Pharmaceutical Preparations