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冰片是传统中药,近年来许多文献报道冰片能提高其他药物的生物利用度,促进其他药物进入血脑屏障,因而冰片与其他药物合用可能产生的药物相互作用受到高度重视,但冰片对肝脏细胞色素P450酶的影响却鲜有报道。本文研究了雄性Wistar大鼠连续灌胃冰片一周对大鼠肝脏CYP2D表达与活性以及对CYP2D探针底物右美沙芬大鼠体内药代动力学的影响。结果表明,冰片(33、100和300 mg·kg-1·d-1)给药一周对大鼠肝脏CYP2D1 m RNA和蛋白表达无明显影响,但却显著诱导了CYP2D活性(P<0.05),分别达到1.71、1.97和2.89倍。此外,与对照组相比,冰片(300 mg·kg-1·d-1)预给药一周组右美沙芬的达峰浓度Cmax降低了10.6%(P>0.05),曲线下面积AUC0-∞减少了27.5%(P<0.01),清除率CL/F增大了41.1%(P<0.01),表观分布容积Vz/F增大了23.1%(P>0.05),表明冰片预给药一周能明显加速CYP2D探针底物右美沙芬的体内清除。由于冰片对大鼠肝脏CYP2D活性的诱导作用,提示当冰片与CYP2D底物药物共用时,可能存在发生代谢性相互作用的风险。
Borneol is a traditional Chinese medicine. In recent years, many reports indicate that borneol can increase the bioavailability of other drugs and promote the entry of other drugs into the blood-brain barrier. Therefore, the potential interactions between borneol and other drugs are highly valued. However, The impact of P450 enzymes is rarely reported. In this paper, we investigated the effects of one-week continuous intragastric administration of borneol on CYP2D expression and activity in rat liver and the pharmacokinetics of CYP2D probe in dextromethorphan rats. The results showed that CYP2D activity was significantly induced by borneol (33, 100 and 300 mg · kg-1 · d-1) for one week on CYP2D1 mRNA and protein expression in rat liver, Respectively, reaching 1.71, 1.97 and 2.89 times. In addition, the C max of dextromethorphan concentration decreased by 10.6% (P> 0.05) in the pre-administration group of borneol (300 mg · kg -1 · d -1) compared with that of the control group. The area under the curve AUC0-∞ (P <0.01). The CL / F clearance rate increased by 41.1% (P <0.01) and the apparent volume of distribution Vz / F increased by 23.1% (P> 0.05) Can significantly accelerate the clearance of CYP2D probe substrate dextromethorphan. Due to the induction of CYP2D activity in rat liver by borneol, it is suggested that there may be a risk of metabolic interaction when borneol is used with CYP2D substrate drug.