Novel direct curve comparison metrics for bioequivalence.
OBJECTIVE
The object of this work was to devise four new direct curve comparison (DCC) metrics and examine each metric's distribution properties and performance characteristics.


METHODS
DCC metrics, Cmax, and AUCi were calculated from two bioequivalence studies of three sustained release carbamazepine formulations, where a range of profile similarity was observed. DCC metric values and their confidence intervals were compared to Cmax and AUCi.


RESULTS
The DCC metrics rho, rhom, deltaa, and deltas, exhibited more favorable distributions than Cmax and AUCi ratios, which were frequently skewed. The DCC metrics performed differently than Cmax and AUCi ratios in profile comparisons due to the nature of the DCC metrics. Unlike Cmax and AUCi, the DCC metrics utilize all data points to directly compare entire profiles. Each DCC metric appears to measure "exposure" in a single assessment. Possible bioequivalence acceptance criteria are: p < or =1.40, rhom, < or =0.35, deltaa, < or =0.27, and deltas < or =0.102.


CONCLUSIONS
These DCC metrics, particularly rhom, are promising bioequivalence metrics for "exposure."
Polli
J E
JE
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore 21201, USA. jpolli@rx.umaryland.edu
McLean
A M
AM
D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics; D016001:Confidence Intervals; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D013810:Therapeutic Equivalency
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D002220:Carbamazepine