Bioequivalence and absolute bioavailability of oblong and coated levomepromazine tablets in CYP2D6 phenotyped subjects.
The bioequivalence and absolute bioavailability of oblong and coated levomepromazine 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 liquid chromatographic method and electrochemical detection. The 2 oral formulations were bioequivalent. After oral administration of oblong and coated levomepromazine tablets the mean serum concentration versus time profiles were similar and the pharmacokinetic parameters showed wide interindividual variations. There was a 21% absolute bioavailability of levomepromazine, indicating a pronounced presystemic metabolism. The total serum clearance and the apparent volume of distribution at steady state were 48 +/- 14 l/min and 980 +/- 213 l, respectively. These pharmacokinetic parameters were also investigated with respect to the CYP2D6 polymorphism, i.e. via dextromethorphan phenotyping of 9 subjects, 3 subjects were poor metabolizers, and 6 extensive metabolizers. The Spearman's rank-ordered correlation analysis did not reveal a significant correlation between the pharmacokinetic parameters AUC, Cmax and t1/2 after oral administration of oblong and coated levomepromazine tablets and the metabolic ratios of dextromethorphan, suggesting that levomepromazine is not metabolized to any major extent by the isoenzyme CYP2D6.
Bagli
M
M
Department of Psychiatry, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
Höflich
G
G
Rao
M L
ML
Langer
M
M
Baumann
P
P
Kolbinger
M
M
Barlage
U
U
Kasper
S
S
Möller
H J
HJ
D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008728:Methotrimeprazine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010641:Phenotype; D011110:Polymorphism, Genetic; D013608:Tablets, Enteric-Coated; D013810:Therapeutic Equivalency
D014150:Antipsychotic Agents; D013608:Tablets, Enteric-Coated; D008728:Methotrimeprazine; D019389:Cytochrome P-450 CYP2D6