Effects of bojungikkitang (a polyherbal formula), on gefitinib pharmacokinetics in rats

Abstract

Gefitinib is mainly used for treatment of non-small cell lung cancers and breast cancers, but many researcher have been interested in the combination therapies due to gefitinib-related toxicities. Bojungikkitang (BJIKT) is a traditional Korean herbal medicine for various tonic effects in patients with poor gastrointestinal functions and conditions debilitated from chronic diseases, which suggests possibility to improve cachexia in cancer patients or the immune system as an adjunctive therapy. Therefore, the pharmacokinetic interactions between gefitinib and BJIKT were examined as a first screening for the combination therapy. One batch of 10 rats received single oral co-administration of gefitinib with BJIKT (combination) or with distilled water (control). Another batch of 10 rats received repeated oral administration of the combination for 9 days after pretreatments with BJIKT for 7 days or control for 9 days after pretreatments with distilled water for 7 days. In the single and repeated co-administration, the gefitinib and BJIKT were used at doses of 50 and 100 mg kg −1, respectively and the co-administration with BJIKT or distilled water was performed within 5 min after gefitinib. The plasma samples were collected time-dependently after the single administration and the initial and last treatment of the repeated administration. The analyzed pharmacokinetic parameters included peak concentration (C max), time to reach the C max, area under the plasma concentration-time curve, half-life and mean residence time to infinity. In the single administration, the gefitinib kinetic curves of plasma concentration were not different between the both of combination and control. There were no differences in the pharmacokinetic parameters between the both. It suggests little interactions between gefitinib and BJIKT. In addition, there were no interactions between gefitinib and BJIKT in the single co-administration after pretreatments for 7 days and even after the repeated co-administration for 9 days. This study provides basic information for the combination therapy of gefitinib with BJIKT.