Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism
Context: Ginkgo leaf tablets (GLTs) and losartan are often simultaneously used for the treatment of hypertension in Chinese clinics. However, the herb–drug interaction between GLT and losartan is still unknown. Objective: This study investigates the effects of GLT on the pharmacokinetics of losartan...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2018-01-01
|
| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2018.1481107 |
| Summary: | Context: Ginkgo leaf tablets (GLTs) and losartan are often simultaneously used for the treatment of hypertension in Chinese clinics. However, the herb–drug interaction between GLT and losartan is still unknown. Objective: This study investigates the effects of GLT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its potential mechanism. Materials and methods: The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10 mg/kg) with or without GLT pretreatment (80 mg/kg/day for 10 days) in Sprague–Dawley rats were determined. In vitro, the effects of GLT on the metabolic stability of losartan were investigated with rat liver microsomes. Results: The Cmax (1.22 ± 0.25 vs 1.85 ± 0.37 μg/mL) and the AUC(0–t) (6.99 ± 1.05 vs 11.94 ± 1.79 mg·h/L) of losartan increased significantly (p < 0.05) with GLT pretreatment, while the Cmax (1.05 ± 0.19 vs 0.72 ± 0.12 μg/mL) of EXP3174 decreased significantly (p < 0.05) compared to the control. The t1/2 of losartan was prolonged significantly from 3.94 ± 0.62 to 4.75 ± 0.52 h (p < 0.05). The metabolic stability of losartan was increased from 37.4 min to 59.6 min with GLT pretreatment. Discussion and conclusions: The results indicate that GLT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the metabolism of losartan. |
|---|---|
| ISSN: | 1388-0209 1744-5116 |