Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition

Xi-feng Zhang; Ju Liu; Feng Ye; Sen-guo Ji; Ni Zhang; Ru-sen Cao; Ling He; Jiang-chuan Wu; Xing-fu Li

doi:10.1007/s11655-014-1710-0

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Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition

OriginalPaper | Updated：2021-08-27

- Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition
- Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition
- 中国结合医学杂志（英文版） 2014年20卷第7期页码：534-539
- Affiliations：
  
  1. Department of Rheumatology, Qilu Hospital, Shandong University,Jinan,China
  2. Department of Rheumatology, Jiujiang No.1 People’s Hospital,Jiangxi Province,Jiujiang,China
  3. Department of Hepatology, the Second Hospital of Shandong University,Jinan,China
  4. Department of Gastroenterology, Jiangxi Hospital of Traditional Chinese Medicine,Nanchang,China
  5. Department of Radiology, Hiser Hospital of Qingdao,Shandong Province,Qingdao,China
- Author bio：
- Funds：
- DOI：10.1007/s11655-014-1710-0
  中图分类号：
- 纸质出版日期：2014，
  
  网络出版日期：2014-1-13，
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Zhang, Xf., Liu, J., Ye, F. et al. Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition., Chin. J. Integr. Med. 20, 534–539 (2014). https://doi.org/10.1007/s11655-014-1710-0

Xi-feng Zhang, Ju Liu, Feng Ye, et al. Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition[J]. Chinese Journal of Integrative Medicine, 2014,20(7):534-539.
Zhang, Xf., Liu, J., Ye, F. et al. Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition., Chin. J. Integr. Med. 20, 534–539 (2014). https://doi.org/10.1007/s11655-014-1710-0 DOI：

Xi-feng Zhang, Ju Liu, Feng Ye, et al. Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition[J]. Chinese Journal of Integrative Medicine, 2014,20(7):534-539. DOI： 10.1007/s11655-014-1710-0.

摘要

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). 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 6β-hydroxylated testosterone (6β-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%. 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). 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.

Abstract

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). In the pharmacokinetics experiment

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

关键词

TriptolidecyclophosphamidepharmacokineticscytochromeP3A4

Keywords

TriptolidecyclophosphamidepharmacokineticscytochromeP3A4

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