Effects of astragaloside IV on the pharmacokinetics of omeprazole in rats
Context: Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics. Objective: This study investigates the effects of AS-IV on the pharmacokinetics of omeprazole in rats. Materials and methods: The pharmacokinetics of orally administered omeprazole...
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Published in | Pharmaceutical biology Vol. 57; no. 1; pp. 449 - 452 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
Taylor & Francis
01.01.2019
Taylor & Francis Ltd Taylor & Francis Group |
Subjects | |
Online Access | Get full text |
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Summary: | Context: Omeprazole and astragaloside IV (AS-IV) are widely used for the treatment of gastric ulcers in China clinics.
Objective: This study investigates the effects of AS-IV on the pharmacokinetics of omeprazole in rats.
Materials and methods: The pharmacokinetics of orally administered omeprazole (2 mg/kg), with or without AS-IV (100 mg/kg/day for 7 days) pretreatment, were investigated in male Sprague-Dawley rats (two groups of six animals each) using LC-MS/MS. A Caco-2 cell transwell model and rat liver microsome incubation systems were also used to support the in vivo pharmacokinetic data and investigate its potential mechanism.
Results: The results indicated that co-administration of AS-IV could decrease the systemic exposure of omeprazole significantly (p < 0.05), including AUC
0-
t
(717.20 ± 177.63 vs. 1166.25 ± 186.65 ng h/mL) and C
max
(272.35 ± 25.81 vs. 366.34 ± 32.57 ng/mL). The t
1/2
of omeprazole also decreased significantly (1.78 ± 0.15 vs. 2.23 ± 0.27 h, p < 0.05). The efflux ratio of omeprazole across the Caco-2 cell transwell model increased significantly from 1.73 to 2.67 (p < 0.05), and the metabolic stability of omeprazole was decreased from 42.6 ± 7.8 to 26.2 ± 5.1 min with the pretreatment of AS-IV (p < 0.05).
Discussion and conclusions: AS-IV could decrease the systemic exposure of omeprazole in rats when AS-IV and omeprazole were co-administered, and it might exert these effects through decreasing the absorption of omeprazole by inducing P-gp, or through accelerating the metabolism of omeprazole in rat liver by inducing the activity of CYP3A4. |
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Bibliography: | The first two authors contributed equally to this work. |
ISSN: | 1388-0209 1744-5116 |
DOI: | 10.1080/13880209.2019.1636828 |