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山柰提取物与西地那非在大鼠体内的药代动力学相互作用。

Pharmacokinetic interaction between Kaempferia parviflora extract and sildenafil in rats.

作者信息

Mekjaruskul Catheleeya, Sripanidkulchai Bungorn

机构信息

Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, 44150, Thailand,

出版信息

J Nat Med. 2015 Apr;69(2):224-31. doi: 10.1007/s11418-014-0882-4. Epub 2015 Jan 8.

Abstract

Kaempferia parviflora (KP) is a plant widely used in Southeast Asia. Its major compounds are 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7,4'-trimethoxylflavone (TMF), and 5,7-dimethoxyflavone (DMF). This study investigated the effect of KP extract on the blood levels and pharmacokinetics of sildenafil co-administration in rats. Rats were randomly assigned to four groups. Groups 1, 2, and 3 were given sildenafil 20 mg/kg daily for 9 days. On days 4-9 of each treatment period, the treated rats received KP extract (250 mg/kg) and vehicle (groups 2 and 3, respectively). Group 4 received KP extract only (250 mg/kg daily for 9 days). Daily blood concentrations of sildenafil, PMF, TMF, and DMF were determined by HPLC to evaluate the daily blood level interactions. Additional blood samples were collected at various times on the last day of treatment to evaluate the pharmacokinetic interactions. The KP extract decreased blood levels of sildenafil on the first day of co-administration by 95 % but the percentage reduction was insignificant on subsequent days. When co-administered with KP extract, the area under the curve (AUC), maximum concentration (C max), and half-life (T 1/2) of sildenafil were decreased by 60-65, 40-52, and 32-54 %, respectively, with the elimination rate constant (K e) increased by 37-77 %. In addition, PMF, TMF, and DMF concentrations and their AUC, C max, T max, K e, and T 1/2 values were changed after co-administration of KP extract and sildenafil.

摘要

小花山柰(KP)是一种在东南亚广泛使用的植物。其主要化合物为3,5,7,3',4'-五甲氧基黄酮(PMF)、5,7,4'-三甲氧基黄酮(TMF)和5,7-二甲氧基黄酮(DMF)。本研究调查了KP提取物对大鼠体内西地那非联合给药时血药浓度及药代动力学的影响。大鼠被随机分为四组。第1、2和3组每天给予20mg/kg西地那非,持续9天。在每个治疗期的第4 - 9天,接受治疗的大鼠分别接受KP提取物(250mg/kg)和赋形剂(第2组和第3组)。第4组仅接受KP提取物(每天250mg/kg,持续9天)。通过高效液相色谱法测定西地那非、PMF、TMF和DMF的每日血药浓度,以评估每日血药浓度的相互作用。在治疗的最后一天的不同时间采集额外的血样,以评估药代动力学相互作用。联合给药第一天,KP提取物使西地那非血药浓度降低了95%,但在随后几天降低的百分比无统计学意义。与KP提取物联合给药时,西地那非的曲线下面积(AUC)、最大浓度(Cmax)和半衰期(T1/2)分别降低了60 - 65%、40 - 52%和32 - 54%,消除速率常数(Ke)增加了37 - 77%。此外,联合给予KP提取物和西地那非后,PMF、TMF和DMF的浓度及其AUC、Cmax、Tmax、Ke和T1/2值均发生了变化。

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