Novel LC-MS/MS method for simultaneous quantification of KW-7158, a new drug candidate for urinary incontinence and bladder hyperactivity, and its metabolites in rat plasma: a pharmacokinetic study in male and female rats.
Arzneimittelforschung
; 62(5): 213-21, 2012 May.
Article
en En
| MEDLINE
| ID: mdl-22344572
ABSTRACT
To investigate the pharmacokinetics of KW-7158 (CAS 214763-95-8), a new drug candidate for urinary incontinence and bladder hyperactivity, in male and female rats, we developed and validated a simultaneous quantification method for KW-7158 and its 2 metabolites, M1 and M2, in plasma using high performance liquid chromatography-tandem mass spectrometry with positive/negative ion-switching scan mode. The method was selective and sensitive to KW-7158, M1 and M2 with overall precision expressed as coefficient of variance less than 11.8% and accuracy (relative error) within ± 13.7% in intra- and inter-assay variability. This method was used to determine the plasma concentration of KW-7158, M1 and M2 after intravenous and oral administration of KW-7158 in male and female rats. KW-7158 was detected as a primary constituent in plasma in both administration routes. M1 was a major metabolite with the concentration ratio of 10-20% of KW-7158, and M2 was a minor metabolite. Pharmacokinetics of KW-7158 after oral administration was considered to be linear at doses from 0.01 to 1 mg/kg. Bioavailability was relatively high with the values of 69.4 ± 17.1% and 82.6 ± 20.0% at a dose of 0.1 mg/kg in male and female rats, respectively. There was a little gender difference in pharmacokinetics of KW-7158 and its metabolites in rats.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Incontinencia Urinaria
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Benzotiepinas
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Vejiga Urinaria Neurogénica
Límite:
Animals
Idioma:
En
Revista:
Arzneimittelforschung
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
ALEMANHA
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ALEMANIA
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DE
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DEUSTCHLAND
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GERMANY