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

Updated：2021-08-27

- Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of CytochromeP3A4 inhibition
- Chinese Journal of Integrative Medicine Vol. 20, Issue 7, Pages: 534-539(2014)
- 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
  CLC：
- Published：2014，
  
  Published Online：13 January 2014，
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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 20(7):534-539(2014)
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 20(7):534-539(2014) 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

references

Du X, Wan X, Cao C. Cyclophosphamide versus mycophenolate mofetil for initial treatment of lupus nephritis. Kindey Int 2013;83:968–969.

Boumpas DT, Austin HA 3rd, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992;340:741–745.

Ruiz-Irastorza G, Danza A, Khamashta M. Treatment of systemic lupus erythematosus: myths, certainties and doubts. Med Clin 2013.

Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996;125:549–557.

Ekhart C, Doodeman VD, Rodenhuis S, Smits PH, Beijnen JH, Huitema AD. Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide. Pharmacogenet Genomics 2008;18:515–523.

Pass GJ, Carrie D, Boylan M, Lorimore S, Wright E, Houston B, et al. Role of hepatic cytochrome p450s in the pharmacokinetics and toxicity of cyclophosphamide: studies with the hepatic cytochrome p450 reductase null mouse. Cancer Res 2005;65:4211–4217.

Ayash LJ, Wright JE, Tretyakov O, Gonin R, Elias A, Wheeler C, et al. Cyclophosphamide pharmacokinetics: correlation with cardiac toxicity and tumor response. J Clin Oncol 1992;10:995–1000.

Wang QX, Shi C, Wu CQ, Yu SZ, Yuan BL, Liao MY. Add-on effects of dexamethasone on cyclophosphamide toxicity in male Wistar rats. Chin J New Drugs (Chin) 2005;14:162–165.

Tao XL, Lipsky PE. The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis clin North Am 2000;26:29–50.

Lin GM, Zhang M, Hou CH. Research progress on Tripterygium wilfordii Hook. Chin Agricult Sci Bull (Chin) 2009;25(23):90–93.

Shui GX, Wan YG, Jiang CM, Zhang HL Chen P, Wang CJ, et al. Progress in Tripterygium wilfordii and its bioactive components in the field of pharmacodynamics and pharmacology. China J Chin Mater Med (Chin) 2010;35:515–520.

Jiao J, Jiang Q. External application of compound Tripterygium wilfordii decreased the activity of rheumatoid arthritis. Chin J Integr Tradit West Med (Chin) 2012;32:1470–1472, 1476.

Wang B, Ma L, Tao X, Lipsky PE. Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription. Arthritis Rheum 2004;50:2995–3003.

Sun TZ, He XF. Efficacy comparision of Tripterygium wilfordii polyglycoside and cyclophosphamide combined with prenisone treatment on idiopathic membranous nephropathy. J Logist Univ China Armed Police Force (Chin) 2012;21:678–681.

Jin N, Gan XD. Clinical analysis of the combination of Tripterygium wilfordii with cyclophosphamide in treatment of refractory lupus nephritis. Zhejiang J Integr Tradit Chin West Med (Chin) 2002;12:346–347.

Zhao L. A clinical comparison on the combination of Tripterygium wilfordii Polyglycoside with cyclophosphamide in treatment of refractory nephrotic syndrome. Hebei Med J (Chin) 2009;31:2160–2161.

Liu SJ, Liu ZX, Zhou L, Ju WZ, Zhang J, Tan HS. Active ingredients of Tripterygium wilfordii impact on P450 activities using a cocktail method. Chin Pharmacol Bull (Chin) 2011;27:276–280.

Yuan R, Madani S, Wei XX, Reynolds K, Huang SM. Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metab Dispos 2002;30:1311–1319.

Chong-Ki Lee, Jun-Shik Choi, Dong-Hyun Choi. Effects of pravastatin on the pharmacokinetic parameters of nimodipine after oral and intravenous administration in rats: possible role of CYP3A4 inhibition by pravastatin. Indian J Pharmacol 2012;44:624–628.

Li XN, Yu N, Zhang JM, Lin WS, Ling XM, Fu G, et al. Quantitative determination of cyclophosphamide in rat plasma using an on-line SPE HPLC-DAD. J Chin Pharm Sci (Chin) 2012;21:156–161.

He ZY, Wu YP, Zhang WT, Wu Q. Determination of cyclophosphamide in plasma using high performance liquid chromatography. China Med Herald (Chin) 2007;4:137–138.

Yu WJ, Huang LJ, Zhu DL. Screening of Chinese material medica possessed inhibitory effect on cytochrome P450 2D6 in liver microsomes of rats. Chin Tradit Herb Drugs (Chin) 2007;38:397–401.

Qu YQ, Liang R, Sun DG, Fang ZZ, Gao ZM, Wang LM. Inhibitory effect of diethylatilbestrol on cytochrom P450 3A4 and cytochrome P450 2C9 in human liver microsomes. Chin J Pharmacol Toxicol (Chin) 2011;25:170–175.

Yu LJ, Pernille D, Katja G, Etienne B, Jodie DH, and David JW. In vivo modulation of alternative pathways of P-450-catalyzed cyclophosphamide metabolism: impact on pharmacokinetics and antitumor activity. J Pharmacol Experiment Therap 1999;288:928–937.

Kelly PA, Wang H, Napoli KL, Kahan BD, Strobel HW. Metabolism of cyclosporine by cytochromes P450 3A9 and 3A4. Eur J Drug Metab Pharmacokinet 1999;24:321–328.

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