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

  • Herb-Drug Interaction
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressa®) 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

Methylcellulose (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, gefitinib (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 monoexponential 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 (Cmax, 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 multipledose 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.

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Authors and Affiliations

  1. College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk, 38430, Republic of Korea

    Kwon-Yeon Weon, Sang Hoon Joo, Eunsook Ma & Seok Won Jeong

  2. School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea

    Min Gi Kim, Tae Hwan Kim, Sun Dong Yoo, Yu Seok Youn & Beom Soo Shin

  3. College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea

    Soyoung Shin

Authors
  1. Kwon-Yeon Weon
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  2. Min Gi Kim
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  3. Soyoung Shin
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  4. Tae Hwan Kim
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  5. Sang Hoon Joo
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  6. Eunsook Ma
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  7. Seok Won Jeong
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  9. Yu Seok Youn
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  10. Beom Soo Shin
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Correspondence to Beom Soo Shin.

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Weon, KY., Kim, M.G., Shin, S. et al. Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal Medications in Rats. Chin. J. Integr. Med. 24, 460–466 (2018). https://doi.org/10.1007/s11655-017-2907-9

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  • DOI: https://doi.org/10.1007/s11655-017-2907-9

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