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Enhanced nimodipine bioavailability after oral administration of nimodipine with morin, a flavonoid, in rabbits

Author:
Choi, Jun Shik, Burm, Jin Pil
Source:
Archives of pharmacal research 2006 v.29 no.4 pp. 333
ISSN:
0253-6269
Subject:
P-glycoproteins, bioavailability, cytochrome P-450, flavonoids, oral administration, rabbits
Abstract:
The aim of this study was to investigate the effect of morin on the bioavailability of nimodipine after administering nimodipine (15 mg/kg) orally to rabbits either co-administered or pretreated with morin (2, 10 and 20 mg/kg). The plasma concentrations of nimodipine in the rabbits pretreated with morin were increased significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) compared with the control, but the plasma concentrations of nimodipine co-administered with morin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations (Cₘₐₓ) of the nimodipine in the rabbits pretreated with morin were significantly higher (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg), but only the Cₘₐₓ of nimodipine co-administered with morin 10 mg/kg was increased significantly (p<0.05). The absolute bioavailability (A.B%) of nimodipine in the rabbits pretreated with morin was significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) higher (54.1–65.0%) than the control (36.7%). The increased bio-availability of nimodipine in the rabbits pretreated with morin might have been resulted from the morin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme by cytochrome P-450 3A4 (CYP 3A4).
Agid:
5482868