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.
Artigo
em Inglês
| 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>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Quinazolinas
/
Fatores de Tempo
/
Sangue
/
Medicamentos de Ervas Chinesas
/
Farmacocinética
/
Cromatografia Líquida
/
Ratos Sprague-Dawley
/
Relação Dose-Resposta a Droga
/
Espectrometria de Massas em Tandem
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Chinese journal of integrative medicine
Ano de publicação:
2018
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS