Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: a possible role of cytochrome P3A4 inhibition.
Chin J Integr Med
; 20(7): 534-9, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24420925
ABSTRACT
OBJECTIVE:
To evaluate the effect of a 10-day course of triptolide (TP) on rat cytochrome (CY) P3A4 activity, and on the pharmacokinetics of cyclophosphamide (CPA).METHODS:
In the pharmacokinetics experiment, rats were orally given 0.9% NaCl solution (n=5) and TP [1.2 (mg/kg·d)] for 10 days and a single dose of CPA was administered intravenously (100 mg/kg) to rats on day 11. Blood samples were collected up to 4 h at predetermined time intervals, the plasma concentration of CPA was determined by high performance liquid chromatography (HPLC) and pharmacokinetic parameters were determined. In the in vitro CYP3A4 activity inhibition research, rat blank liver microsomes were divided into 3 groups a control group, a TS (5 µL, 200 µmol/L) with TP (5 µL, 12.5 µmol/L) group, a TS with ketoconazole (5 µL, 1 µmol/L) group. Concentration of 6ß-hydroxylated testosterone (6ß-OHT) in liver microsomes was measured by HPLC and the activity of CYP 3A4 was calculated through the following formula Einhibitor/Econtrol × 100%=Cinhibitor/Ccontrol × 100%.RESULTS:
Compared with the control group, the area under the plasma concentration-time curve (AUC0-∞) of CPA was significantly increased by 229.05% pretreated with TP (P<0.01). Peak plasma concentrations (Cmax) of CPA was significantly increased and plasma half-life was correspondingly extended. The CYP3A4 activity was significantly inhibited by ketoconazole 93.5%±0.2% and TP 84.6%±0.3% compared with the control group (P<0.01 and P<0.05, respectively).CONCLUSION:
Our results strongly suggested that long-term oral intake of TP can distinctly inhibit the CYP3A4 activity and this inhibition evidently decrease the formation of toxic metabolites of CPA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenantrenos
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Ciclofosfamida
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Interações Ervas-Drogas
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Diterpenos
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Citocromo P-450 CYP3A
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Inibidores do Citocromo P-450 CYP3A
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Imunossupressores
Limite:
Animals
Idioma:
En
Revista:
Chin J Integr Med
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China