Metabolism of dimetindene in rats.
Arzneimittelforschung
; 45(10): 1086-92, 1995 Oct.
Article
en En
| MEDLINE
| ID: mdl-8595065
The preparative separation of dimetindene (CAS 5636-83-9) enantiomers was achieved by fractionated crystallization of the diastereomeric tartrate salts. HPLC on alpha-AGP (alpha 1-acid glycoprotein) was used for confirmation of the enantiomeric purity. After administration of the enantiomers to rats the AUC and Cmax of S(+) dimetindene and (-)N-demethyldimetindene were slightly increased. In agreement with the serum concentration data significantly more (-)N-demethyldimethindene was excreted into urine after administration of the individual enantiomers. S(+) dimetindene was metabolised to a lesser extent in vivo (see above) as well as in vitro in rat liver homogenate. After prior enzyme induction conversion of the enantioselectivity with respect to unmetabolised dimetindene occurred. 6-Methoxydimetindene, 6-hydroxydimetindene and 6-hydroxy-N-demethyldimetindene were synthesized. 6-Methoxydimetindene is likely to be a metabolite since the retention times of synthetic compound and the substance extracted from serum and urine are identical. The formation of 6-hydroxy-N-demethyldimetindene was proved for the first time by comparison of the mass spectra of metabolite isolated from in vitro incubations and synthetic compound after derivatisation with acetic anhydride.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dimetindeno
/
Antagonistas de los Receptores Histamínicos H1
Límite:
Animals
Idioma:
En
Revista:
Arzneimittelforschung
Año:
1995
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Alemania