Enantioselective biotransformation of the chiral antihistaminic drug dimethindene in humans and rats.
Arzneimittelforschung
; 47(5): 653-8, 1997 May.
Article
en En
| MEDLINE
| ID: mdl-9205781
The biotransformation of dimethindene (CAS 5636-83-9, dimethindene maleate, CAS 3614-69-5) after oral administration was determined in urine using an HPLC gradient method. Besides the phase I metabolites the conjugates of the hydroxylated metabolites with glucuronic and/or sulfuric acid were quantitatively determined after enzymatic deconjugation. The cumulative excretion of 6-hydroxydimethindene and 6-hydroxy-N-demethyldimethindene in human urine after hydrolysis of the conjugates ranged from 18 to 23% of the administered dose, independent of the amount of the dose applied. The results indicate that conjugated 6-hydroxydimethindene is the main metabolite of dimethindene. Increasing doses of 5 to 20 mg dimethindene maleate did not affect the relative amount of the excreted metabolites but changed the ratio of 6-hydroxydimethindene to 6-hydroxy-N-demethyldimethindene from 3:1 to 1:1. In rats about 4 to 8% of the administered dose of dimethindene was excreted as dimethindene-N-oxide which is the main metabolite in rat urine. After administration of R-(-)-dimethindene the elimination of all metabolites was 2 to 3 fold higher compared to the administration of the S-(+)-enantiomer. By chiral HPLC, in 10 human volunteers a stereoselective elimination of N-demethyl-dimethindene after oral administration of racemic dimethindene with the predominant excretion of the R-(-)-enantiomer was observed.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dimetindeno
/
Antagonistas de los Receptores Histamínicos H1
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Arzneimittelforschung
Año:
1997
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Alemania