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 ...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.展开更多
基金Supported by the Comprehensive and Interactive Medicine InstituteNational Research Foundation of Korea(No.2012R1A2A2A02044997)
文摘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.
