Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal Medications in Rats

作     者：Kwon-Yeon Weon Min Gi Kim Soyoung Shin Tae Hwan Kim Sang Hoon Joo Eunsook Ma Seok Won Jeong Sun Dong Yoo Yu Seok Youn Beom Soo Shin 

作者机构：College of PharmacyCatholic University of Daegu School of PharmacySungkyunkwan University College of PharmacyWonkwang University 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2018年第24卷第6期

页      面：460-466页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1005[医学-中医学] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：Supported by the Comprehensive and Interactive Medicine Institute National Research Foundation of Korea(No.2012R1A2A2A02044997) 

主　　题：herb-drug interaction pharmacokinetics gefitinib Guipi Decoction Bawu Decoction 

摘      要：Objective： To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib （Iressae） and the oriental medications Guipi Decoction （归脾汤, GPD, Guibi-tang in Korean） and Bawu Decoction （八物汤, BWD, Palmul-tang in Korean）. Methods： Methylceliulose （MC, control）, GPD （1,200 mg/kg）, or BWD （6,000 mg/kg） was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib （10 mg/kg） was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib （10 mg/kg） was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results： Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration （Crux, P〈0.05） and area under the curve （P〈0.05）, and a delayed time to reach Cmax （Tmax, P〈0.01） were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions： BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.