Abstract
This study was performed to evaluate the potential drug–herb interaction between the conventional anti-cancer drug, gefitinib, and the herbal medication, Angelica gigas (AG) extract. One group of rats received a single intravenous (IV) dose of gefitinib (10 mg/kg) to determine its basic pharmacokinetics. Another group received a single oral dose of gefitinib (10 mg/kg) after pretreatment with saline or AG extract (500 mg/kg). The third group received an oral dose of gefitinib after pretreatment with saline or AG extract daily for 7 days. In addition, fecal and urinary recovery of gefitinib after IV and oral administration was evaluated. Gefitinib concentrations were determined using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and the pharmacokinetic parameters were estimated by non-compartmental analysis. In addition, inhibition by AG of CYP3A4, the primary enzyme responsible for the metabolism of gefitinib, was evaluated. The results indicated that the pharmacokinetic parameters of gefitinib following single and multiple doses were not significantly affected by pretreatment with AG extract. Fecal and urinary recovery of gefitinib was not significantly different between groups, and AG extract did not inhibit CYP3A4 activity until the concentration reached 600 μg/mL. Therefore, the data indicated that gefitinib was not significantly affected by co-treatment with AG extract.
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Acknowledgements
All authors (H. R. Kim, S. H. Joo, T. S. Koo) declare that they have no conflict of interest. This study was financially supported by a Grant [CIMI-15-02-05] from Ministry of Health and Welfare of Korea and Chungnam National University.
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Kim, HR., Jeong, JW., Joo, S.H. et al. Effects of Angelica gigas extract on the oral pharmacokinetics of gefitinib in rats. J. Pharm. Investig. 48, 295–300 (2018). https://doi.org/10.1007/s40005-017-0315-y
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DOI: https://doi.org/10.1007/s40005-017-0315-y