In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 60, No. 7 ( 2010-02-18), p. 843-851
Abstract:
It has been reported that omeprazole is mainly metabolized via hepatic cytochrome P450 (CYP) 1A1/2, CYP2D1 and CYP3A1/2 in male Sprague-Dawley rats, and the expression of hepatic CYP3A1 is increased in male Sprague-Dawley rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the metabolism of omeprazole would be expected to increase in U-ARF rats. After intravenous administration of omeprazole (20 mgkg−1) to U-ARF rats, the area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly reduced (371 vs 494 μg min mL−1), possibly due to the significantly faster non-renal clearance (56.6 vs 41.2 mL min−1 kg−1) compared with control rats. This could have been due to increased expression of hepatic CYP3A1 in U-ARF rats. After oral administration of omeprazole (40 mg kg−1) to U-ARF rats, the AUC was also significantly reduced (89.3 vs 235 μg min mL−1) compared with control rats. The AUC difference after oral administration (62.0% decrease) was greater than that after intravenous administration (24.9% decrease). This may have been primarily due to increased intestinal metabolism of omeprazole caused by increased expression of intestinal CYP1A and 3A subfamilies in U-ARF rats, in addition to increased hepatic metabolism.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/jpp.60.7.0005
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
Permalink