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Influence of quercetin on amiodarone pharmacokinetics and biodistribution in rats.

最大值 药代动力学 药理学 生物利用度 槲皮素 CYP3A4型 医学 加药 化学 治疗指标 药品 细胞色素P450 抗氧化剂 内科学 新陈代谢 生物化学
作者
Ejaz Ahmad,Muhammad Jahangir,Nadeem Irfan Bukhari,Josephine Khan,Asma Sarwar,Tariq Aziz,Ghulam Nabi,Mohammed Alharbi,H A Thamer,Abdullah F. Alasmari
出处
期刊:PubMed 卷期号:27 (23): 11211-11221 被引量:3
标识
DOI:10.26355/eurrev_202312_34561
摘要

Amiodarone (AMD), a drug of choice to treat cardiac arrhythmias, has a narrow therapeutic index (NTI). It inhibits CYP3A4, CYP2C9, and CYP2D6 enzymes. Quercetin (QUE), a pharmacologically important bioflavonoid in vegetables and fruits, is important in treating cardiovascular comorbidities. QUE alters the bioavailability of drugs used concurrently by dual inhibition of P-glycoproteins (P-gp) and cytochrome (CYP) enzyme systems. The current study aimed to investigate the pre-treatment and co-administration effect of QUE on AMD pharmacokinetics in rats.Two separate animal trials (I and II) were planned to probe the effect of QUE on AMD pharmacokinetics by following previously cited studies. The pre-treatment group received oral doses of QUE for 14 days, and a single dose of AMD on the 15th day. Rats were administered single doses of QUE (20 mg/kg) and AMD (50 mg/kg) concurrently in a carboxymethylcellulose (CMC) in the co-administration study. Blood was collected at pre-determined time points. AMD was quantified by HPLC, and data was analyzed by PK solver software.In the pre-treated group, peak plasma concentration (Cmax) and area under the curve (AUC0-∞) of AMD were increased by 45.52% and 13.70%, respectively, while time to achieve maximum concentration (tmax), half-life (t1/2) and clearance (CL) were declined by 35.72%, 16.75%, and 11.0% respectively compared to the control. In the co-administered group, compared to controls, Cmax and AUC0-∞ were elevated to 12.90% and 7.80%, respectively, while tmax, t1/2, and CL declined by 16.70%, 2.35%, and 13.40%. Further, AMD was increased in lung tissue of both treated groups, relative to the respective controls.A notable pharmacokinetic drug interaction between QUE and AMD was observed in rats and warrants possible drug interaction study in humans, suggesting AMD dose adjustment specifically in patients with arrhythmia having a pre-treatment history and simultaneous administration of QUE-containing products.
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