Abstract
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.
Highlights
Losartan is the first nonpeptide angiotensin II receptor blocker used in hypertension and diabetic nephropathy (Klishadi et al 2015)
The results indicate that Ginkgo leaf tablets (GLTs) might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the metabolism of losartan
Group B was pretreated with GLT solutions at a dose of 80 mg/kg/day for 10 days before the administration of losartan, and losartan were orally administered to rats by gavage at a dose of 10 mg/kg
Summary
Losartan is the first nonpeptide angiotensin II receptor blocker used in hypertension and diabetic nephropathy (Klishadi et al 2015). The clinical hypotensive activity is predominantly mediated by the active metabolite EXP3174, losartan itself exhibits good efficacy (Varshney et al 2013). Because of its good anti-hypertension effect, losartan has been one of the anti-hypertension drug most frequently used for the prevention and control of hypertension in the clinic (Yasar et al 2008; Yang et al 2011). Ginkgo leaf tablet (GLT) is an effective traditional Chinese multi-herbal formula which is widely used in treating ischemic cerebrovascular disease in the clinic (Lin et al 2003; Chung et al 2006; Yang et al 2017). Losartan and GLT are often simultaneously used for the treatment of hypertension in Chinese clinics. It is essential to investigate the effects of GLT on the pharmacokinetics of losartan and its potential mechanism
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