금은화 추출물이 폐암치료제 gefitinib의 약물동태에 미치는 영향

Effects of Lonicera japonica extract on the Pharmacokinetics of Gefitinib in Rats

The objective of this study was to estimate the potential herb drug interaction between gefitinib and Lonicera japonica (LJ) by evaluating changes in gefitinib pharmacokinetics following single and multiple oral doses of LJ in rats. Firstly, to determine basic pharmacokinetics of gefitinib, rat pharmacokinetics after 3, 10 and 30 mg/kg single intravenous and oral administration of gefitinib was executed. Secondly, single and 7-day repeated oral dose pharmacokinetics of gefitinib(10 mg/kg) after pretreatment with saline or LJ extract (500 mg/kg) were performed. In addition, the effect of fecal and urinary recovery after co-treatment with LJ and the inhibition of CYP3A4 by LJ was evaluated. Gefitinib showed dose-independent pharmacokinetics at intravenous and oral doses of 3−30 mg/kg and the pharmacokinetic parameters of gefitinib following single and multiple doses were not significantly affected by pretreatment with LJ extract. Fecal and urinary recovery of gefitinib was not significantly different between groups and LJ extract did not inhibit CYP3A4, main metabolic enzyme of gefitinib, activity until the concentration reached 300 μg/mL. These indicated that pharmacokinetics of gefitinib was not significantly affected by co-treatment with LJ extract.