Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal Medications in Rats / 中国结合医学杂志
Chinese journal of integrative medicine
;
(12): 460-466, 2018.
Article
in English
| WPRIM
| ID: wpr-687930
ABSTRACT
<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 (C, P<0.05) and area under the curve (P<0.05), and a delayed time to reach C (T, P<0.01) were observed in both single- and multipledose BWD-pretreated rats compared with the control rats.</p><p><b>CONCLUSIONS</b>BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Quinazolines
/
Time Factors
/
Blood
/
Drugs, Chinese Herbal
/
Pharmacokinetics
/
Chromatography, Liquid
/
Rats, Sprague-Dawley
/
Dose-Response Relationship, Drug
/
Tandem Mass Spectrometry
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Chinese journal of integrative medicine
Year:
2018
Type:
Article
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