Auto-induction of phase I and phase II metabolism of artemisinin in healthy Chinese subjects after oral administration of a new artemisinin-piperaquine fixed combination

详细信息    查看全文

• 作者：Meitong Zang (1)
  Fanping Zhu (1)
  Xinxiu Li (1)
  Aijuan Yang (1)
  Jie Xing (1)
  
  1. School of Pharmaceutical Sciences ; Shandong University ; 44# West Wenhua Road ; Jinan ; 250012 ; P R China
  
• 关键词：Artemisinin ; Auto ; induction metabolism ; Healthy Chinese ; CYP activity
• 刊名：Malaria Journal
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：13
• 期：1
• 全文大小：358 KB
• 参考文献：1. Zhu, C, Cook, SP (2012) A concise synthesis of (+)-artemisinin. J Am Chem Soc 134: pp. 13577-13579 CrossRef
  2. Paddon, CJ, Westfall, PJ, Pitera, DJ, Benjamin, K, Fisher, K, McPhee, D, Leavell, MD, Tai, A, Main, A, Eng, D, Polichuk, DR, Teoh, KH, Reed, DW, Treynor, T, Lenihan, J, Fleck, M, Bajad, S, Dang, G, Dengrove, D, Diola, D, Dorin, G, Ellens, KW, Fickes, S, Galazzo, J, Gaucher, SP, Geistlinger, T, Henry, R, Hepp, M, Horning, T, Iqbal, T (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496: pp. 528-532 CrossRef
  3. Salman, S, Page-Sharp, M, Batty, KT, Kose, K, Griffin, S, Siba, PM, Ilett, KF, Mueller, I, Davis, TM (2012) Pharmacokinetic comparison of two piperaquine-containing artemisinin combination therapies in Papua New Guinean children with uncomplicated malaria. Antimicrob Agents Chemother 56: pp. 3288-3297 CrossRef
  4. Krudsood, S, Tangpukdee, N, Thanchatwet, V, Wilairatana, P, Srivilairit, S, Pothipak, N, Jianping, S, Guoqiao, L, Brittenham, GM, Looareesuwan, S (2007) Dose ranging studies of new artemisinin-piperaquine fixed combinations compared to standard regimens of artemisisnin combination therapies for acute uncomplicated falciparum malaria. Southeast Asian J Trop Med Public Health 38: pp. 971-978
  5. Zhu, DY, Huang, BS, Chen, ZL, Yin, ML, Yang, YM, Dai, ML, Wang, BD, Huang, ZH (1983) Isolation and identification of the metabolite of artemisinin in human (in Chinese). Zhongguo Yao Li Xue Bao 4: pp. 194-197
  6. Svensson, US, M盲ki-Jouppila, M, Hoffmann, KJ, Ashton, M (2003) Characterisation of the human liver in vitro metabolic pattern of artemisinin and auto-induction in the rat by use of nonlinear mixed effects modelling. Biopharm Drug Dispos 24: pp. 71-85 CrossRef
  7. Liu, T, Du, F, Wan, Y, Zhu, F, Xing, J (2011) Rapid identification of phase I and II metabolites of artemisinin antimalarials using LTQ-Orbitrap hybrid mass spectrometer in combination with online hydrogen/deuterium exchange technique. J Mass Spectrom 46: pp. 725-733 CrossRef
  8. Hien, TT, Hanpithakpong, W, Truong, NT, Dung, NT, Toi, PV, Farrar, J, Lindegardh, N, Tarning, J, Ashton, M (2011) Orally formulated artemisinin in healthy fasting Vietnamese male subjects: a randomized, four-sequence, open-label, pharmacokinetic crossover study. Clin Ther 33: pp. 644-654 CrossRef
  9. Ashton, M, Hai, TN, Sy, ND, Huong, DX, Van Huong, N, Ni锚u, NT, C么ng, LD (1998) Artemisinin pharmacokinetics is time-dependent during repeated oral administration in healthy male adults. Drug Metab Dispos 26: pp. 25-27
  10. Gordi, T, Huong, DX, Hai, TN, Nieu, NT, Ashton, M (2002) Artemisinin pharmacokinetics and efficacy in uncomplicated-malaria patients treated with two different dosage regimens. Antimicrob Agents Chemother 46: pp. 1026-1031 CrossRef
  11. Gupta, S, Svensson, US, Ashton, M (2001) In vitro evidence for auto-induction of artemisinin metabolism in the rat. Eur J Drug Metab Pharmacokinet 26: pp. 173-178 CrossRef
  12. Simonsson, US, Jansson, B, Hai, TN, Huong, DX, Tybring, G, Ashton, M (2003) Artemisinin autoinduction is caused by involvement of cytochrome P450 2B6 but not 2C9. Clin Pharmacol Ther 74: pp. 32-43 CrossRef
  13. Xing, J, Kirby, BJ, Whittington, D, Wan, Y, Goodlett, DR (2012) Evaluation of CYPs inhibition and induction by artemisinin antimalarials in human liver microsomes and primary human hepatocytes. Drug Metab Dispos 40: pp. 1757-1764 CrossRef
  14. Svensson, US, Ashton, M (1999) Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol 48: pp. 528-535 CrossRef
  15. Li, XQ, Bj枚rkman, A, Andersson, TB, Gustafsson, LL, Masimirembwa, CM (2003) Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol 59: pp. 429-442 CrossRef
  16. Asimus, S, Elsherbiny, D, Hai, TN, Jansson, B, Huong, NV, Petzold, MG, Simonsson, US, Ashton, M (2007) Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in healthy subjects. Fundam Clin Pharmacol 21: pp. 307-316 CrossRef
  17. Svensson, US, Ashton, M, Trinh, NH, Bertilsson, L, Dinh, XH, Nguyen, VH, Nguyen, TN, Nguyen, DS, Lykkesfeldt, J, Le, DC (1998) Artemisinin induces omeprazole metabolism in human beings. Clin Pharmacol Ther 64: pp. 160-167 CrossRef
  18. Mihara, K, Svensson, US, Tybring, G, Hai, TN, Bertilsson, L, Ashton, M (1999) Stereospecific analysis of omeprazole supports artemisinin as a potent inducer of CYP2C19. Fundam Clin Pharmacol 13: pp. 671-675 CrossRef
  19. Asimus, S, Hai, TN, Van Huong, N, Ashton, M (2008) Artemisinin and CYP2A6 activity in healthy subjects. Eur J Clin Pharmacol 64: pp. 283-292 CrossRef
  20. Burk, O, Piedade, R, Ghebreghiorghis, L, Fait, JT, Nussler, AK, Gil, JP, Windsh眉gel, B, Schwab, M (2012) Differential effects of clinically used derivatives and metabolites of artemisinin in the activation of constitutive androstane receptor isoforms. Br J Pharmacol 167: pp. 666-681 CrossRef
  21. Kenny, JR, Chen, L, McGinnity, DF, Grime, K, Shakesheff, KM, Thomson, B, Riley, R (2008) Efficient assessment of the utility of immortalized Fa2N-4 cells for cytochrome P450 (CYP) induction studies using multiplex quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and substrate cassette methodologies. Xenobiotica 38: pp. 1500-1517 CrossRef
  22. McGinnity, DF, Berry, AJ, Kenny, JR, Grime, K, Riley, RJ (2006) Evaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes. Drug Metab Dispos 34: pp. 1291-1300 CrossRef
  23. Qiu, F, Wang, G, Zhang, R, Sun, J, Jiang, J, Ma, Y (2010) Effect of danshen extract on the activity of CYP3A4 in healthy volunteers. Br J Clin Pharmacol 69: pp. 656-662 CrossRef
  24. Qin, WJ, Zhang, W, Liu, ZQ, Chen, XP, Tan, ZR, Hu, DL, Wang, D, Fan, L, Zhou, HH (2012) Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men. Br J Clin Pharmacol 74: pp. 999-1004 CrossRef
  25. Kim, H, Bae, SK, Park, SJ, Shim, EJ, Kim, HS, Shon, JH, Liu, KH, Shin, JG (2010) Effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, in healthy subjects. Br J Clin Pharmacol 70: pp. 126-131 CrossRef
  26. Nordmark, A, Andersson, A, Baranczewski, P, Wanag, E, St氓hle, L (2014) Assessment of interaction potential of AZD2066 using in vitro metabolism tools, physiologically based pharmacokinetic modelling and in vivo cocktail data. Eur J Clin Pharmacol 70: pp. 167-178 CrossRef
  27. Burk, O, Arnold, KA, Nussler, AK, Schaeffeler, E, Efimova, E, Avery, BA, Avery, MA, Fromm, MF, Eichelbaum, M (2005) Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol 67: pp. 1954-1965 CrossRef
  
• 刊物主题：Parasitology; Infectious Diseases; Tropical Medicine;
• 出版者：BioMed Central
• ISSN：1475-2875

文摘

Background Artequick is a relatively inexpensive artemisinin (Qing-hao-su; QHS)-based combination therapy (ACT) that contains QHS and piperaquine (PQ), which has not been widely used because of the decreased concentration level of QHS after repeated oral administrations for five to seven days as a monotherapy. This study was designed to evaluate the potential auto-induction metabolism of QHS in healthy Chinese adults after a two-day oral administration of QHS-PQ. The effect of QHS-PQ on the activity of the CYP2B6 and CYP3A4 was also investigated. Methods Fourteen healthy Chinese subjects received two-day oral doses of QHS-PQ (Artequick). A two-drug cocktail consisting of bupropion and midazolam was used to assess the activities of CYP2B6 and CYP3A, respectively. Plasma samples were analysed for QHS and its phase I/II metabolites, probe drugs and their metabolites, using a validated liquid chromatography tandem mass spectrometric (LC-MS) method. Results Four major phase I metabolites of QHS (M1-M3 and deoxy-QHS) and two subsequent phase II metabolites (M4-M5) were detected in human plasma after oral administrations of QHS-PQ. The AUC 0-t of the QHS and its phase I metabolites decreased significantly (P P 0-t ratio of all phase I metabolites to QHS, increased 1.5-fold after the repeated dose (P Conclusions The auto-induction of both phase I and phase II metabolism of QHS was present in healthy Chinese subjects after a recommended two-day oral dose of QHS-PQ. The auto-induction metabolism also existed for phase I metabolites of QHS. The enzyme activity of CYP2B6 and CYP3A4 was induced after the two-day oral doses of QHS-PQ. Based on these results, the alternative common three-day regimen for QHS-PQ could probably lead to lower bioavailability of QHS and higher potential of drug-drug interaction caused by the induction of drug-metabolizing enzymes.