Kwon-Yeon Weon1, Min Gi Kim2, Soyoung Shin3, Tae Hwan Kim2, Sang Hoon Joo1, Eunsook Ma1, Seok Won Jeong1, Sun Dong Yoo2, Yu Seok Youn2, Beom Soo Shin4. 1. College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk, 38430, Republic of Korea. 2. School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea. 3. College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea. 4. School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea. bsshin@skku.edu.
Abstract
OBJECTIVE: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressa®) and the oriental medications Guipi Decoction (, GPD, Guibi-tang in Korean) and Bawu Decoction (, 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.
OBJECTIVE: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressa®) and the oriental medications Guipi Decoction (, GPD, Guibi-tang in Korean) and Bawu Decoction (, 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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