BIOEQUIVALENCE AND ABSOLUTE BIOAVAILABILITY OF OBLONG AND COATED LEVOMEPROMAZINE TABLETS IN CYP2D6 PHENOTYPED SUBJECTS

The bioequivalence and absolute bioavailability of oblong and coated l evomepromazine tablets were studied in 12 healthy volunteers. A 1-hour intravenous infusion served as the reference. Serum concentrations of levomepromazine were quantified with a specific high-performance liqu id chromatographic method and electrochemical detection. The 2 oral fo rmulations were bioequivalent. After oral administration of oblong and coated levomepromazine tablets the mean serum concentration versus ti me profiles were similar and the pharmacokinetic parameters showed wid e interindividual variations. There was a 21% absolute bioavailability of levomepromazine, indicating a pronounced presystemic metabolism. T he total serum clearance and the apparent volume of distribution at st eady state were 48 +/- 14 l/min and 980 +/- 213 1, respectively. These pharmacokinetic parameters were also investigated with respect to the CYP2D6 polymorphism, i.e. via dextromethorphan phenotyping of 9 subje cts, 3 subjects were poor metabolizers, and 6 extensive metabolizers. The Spearman's rank-ordered correlation analysis did not reveal a sign ificant correlation between the pharmacokinetic parameters AUG, C-max and t(1/2) after oral administration of oblong and coated levomepromaz ine tablets and the metabolic ratios of dextromethorphan, suggesting t hat levomepromazine is not metabolized to any major extent by the isoe nzyme CYP2D6.