Carbamazepine: a bioequivalence study and limited sampling modeling.
OBJECTIVE
To assess the bioequivalence of 2 formulations of carbamazepine and to develop and validate limited sampling strategy (LSS) models for estimating the area under the plasma concentration-time curve (AUC0-infinity) and the peak plasma concentration (Cmax) of carbamazepine.


METHODS
Twenty-four (12 men, 12 women) healthy volunteers received single oral doses (400 mg) of carbamazepine, as reference and test conventional-release formulations, in a standard 2-sequence, 2-period crossover design. Bioequivalence assessment was based on the individual ratios of log-transformed values of AUC0-infinity and Cmax LSS modeling was developed in a training set of 12 randomly assigned volunteers and was validated on the other 12 subjects (validation set).


RESULTS
Carbamazepine AUC0-infinity and Cmax can be accurately predicted (R2 = 0.89 - 0.95, precision = 2.6 - 7.2%) by single-point (72 h) and 2-point LSS models (6, 32 h), respectively. Bioequivalence assessments based on LSS-derived AUC0-infinity and Cmax provided results similar to those obtained using all the concentration-in-plasma data points, and indicated that the 2 formulations are bioequivalent.


CONCLUSIONS
One-and 2-point LSS models provided accurate estimates of carbamazepine's AUC0-infinity and Cmax, and allowed correct assessment of bioequivalence between the formulations studied.
D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D013810:Therapeutic Equivalency
D000927:Anticonvulsants; D002220:Carbamazepine