The Evaluation of CYP2B6 Inhibition by Artemisinin Antimalarials in Recombinant Enzymes and Human Liver Microsomes

Drug Metabolism Letters

Volumn 6, Issue 4, 2013, Pages 247-257

  Ericsson, Therese ^a   Masimirembwa, Collen ^b   Äbelö, Angela ^a   Ashton, Michael ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b African Institute of Biomedical Science and Technology   (Zimbabwe)

Author keywords

Artemether; Artemisinin; Cytochrome P450 2B6; Dihydroartemisinin; Enzyme inhibition; Human liver microsomes; In vitro

Indexed keywords

ANTIMALARIAL AGENT; ARTEMETHER; ARTEMISININ; CYTOCHROME P450 2B6; DIHYDROARTEMISININ; EFAVIRENZ; KETOCONAZOLE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; TICLOPIDINE;

AREA UNDER THE CURVE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME KINETICS; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; INCUBATION TIME; LIVER MICROSOME; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL;

ANTIMALARIALS; ARTEMISININS; ARYL HYDROCARBON HYDROXYLASES; DRUG INTERACTIONS; ENZYME INHIBITORS; HUMANS; MICROSOMES, LIVER; OXIDOREDUCTASES, N-DEMETHYLATING; RECOMBINANT PROTEINS;

EID: 84884238048     PISSN: 18723128     EISSN: None     Source Type: Journal    
DOI: 10.2174/1872312811206040004     Document Type: Article

References (48)

1. Lin, J. H.; Lu, A. Y. Inhibition and induction of cytochrome P450 and the clinical implications. Clin. Pharmacokinet., 1998, 35 (5), 361-90.
2. Roederer, M. W., Cytochrome P450 enzymes and genotype-guided drug therapy. Curr. Opin. Mol. Ther., 2009, 11 (6), 632-40.
3. Krippendorff, B. F.; Lienau, P.; Reichel, A.; Huisinga, W. Optimizing classification of drug-drug interaction potential for CYP450 isoenzyme inhibition assays in early drug discovery. J. Biomol. Screen, 2007, 12 (1), 92-9.
4. Atkinson, A.; Kenny, J. R.; Grime, K., Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis. Drug Metab. Dispos., 2005, 33 (11), 1637-47.
5. Smith, D. A.; Abel, S. M.; Hyland, R.; Jones, B. C. Human cytochrome P450s: selectivity and measurement in vivo. Xenobiotica, 1998, 28 (12), 1095-128.
6. Ekins, S.; VandenBranden, M.; Ring, B. J.; Wrighton, S. A. Examination of purported probes of human CYP2B6. Pharmacogenetics, 1997, 7 (3), 165-79.
7. Turpeinen, M.; Raunio, H.; Pelkonen, O. The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico. Curr. Drug Metab., 2006, 7 (7), 705-14.
8. Hidestrand, M.; Oscarson, M.; Salonen, J. S.; Nyman, L.; Pelkonen, O.; Turpeinen, M.; Ingelman-Sundberg, M. CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes. Drug Metab. Dispos., 2001, 29 (11), 1480-4.
9. Ward, B. A.; Gorski, J. C.; Jones, D. R.; Hall, S. D.; Flockhart, D. A.; Desta, Z. The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J. Pharmacol. Exp. Ther., 2003, 306 (1), 287-300.
10. U S Food and Drug Administration (FDA), Guidance for industry: drug interaction studies-study design, data analysis, and implications for dosing and labeling.
11. Lewison, G.; Srivastava, D., Malaria research, 1980-2004, and the burden of disease. Acta Trop., 2008, 106 (2), 96-103.
12. Tuteja, R. Malaria-an overview. FEBS, J., 2007, 274 (18), 4670-9.
13. WHO, Malaria; Health topics. World Health Organization (WHO): 2010; Vol. 2012, p Health topics; Malaria.
14. AIDS Epidemic Update December 2009 World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS).
15. Hollenberg, P. F. Characteristics and common properties of inhibitors, inducers, and activators of CYP enzymes. Drug Metab. Rev., 2002, 34 (1-2), 17-35.
16. Zhou, Z. W.; Zhou, S. F. Application of mechanism-based CYP inhibition for predicting drug-drug interactions. Expert Opin. Drug Metab. Toxicol., 2009, 5 (6), 579-605.
17. Nishiya, Y.; Hagihara, K.; Ito, T.; Tajima, M.; Miura, S.; Kurihara, A.; Farid, N. A.; Ikeda, T. Mechanism-based inhibition of human cytochrome P450 2B6 by ticlopidine, clopidogrel, and the thiolactone metabolite of prasugrel. Drug Metab. Dispos., 2009, 37 (3), 589-93.
18. Thelingwani, R. S.; Zvada, S. P.; Dolgos, H.; Ungell, A.-L.; Masimirembwa, C. M. In vitro and in silico identification and characterization of thiabendazole as a mechanism-based inhibitor of CYP1A2 and simulation of possible pharmacokinetic drug-drug interactions. Drug Metab. Dispos., 2009, 37 (6), 1286-94.
19. Ito, K.; Brown, H. S.; Houston, J. B. Database analyses for the prediction of in vivo drug-drug interactions from in vitro data. Br. J. Clin. Pharmacol., 2004, 57 (4), 473-86.
20. Ito, K.; Iwatsubo, T.; Kanamitsu, S.; Nakajima, Y.; Sugiyama, Y. Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. Annu Rev Pharmacol. Toxicol., 1998, 38, 461-99.
21. Ito, K.; Iwatsubo, T.; Kanamitsu, S.; Ueda, K.; Suzuki, H.; Sugiyama, Y. Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver. Pharmacol. Rev., 1998, 50 (3), 387-412.
22. Alin, M.; Ashton, M.; Kihamia, C.; Mtey, G.; Björkman, A. Clinical efficacy and pharmacokinetics of artemisinin monotherapy and in combination with mefloquine in patients with falciparum malaria. Br. J. Clin. Pharmacol., 1996, 41 (6), 587-92.
23. Alin, M.; Ashton, M.; Kihamia, C.; Mtey, G.; Björkman, A. Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients. Trans. R. Soc. Trop. Med. Hyg., 1996, 90 (1), 61-65.
24. Ashton, M.; Nguyen, D. S.; Nguyen, V. H.; Gordi, T.; Trinh, N. H.; Dinh, X. H.; Nguyen, T. N.; Le, D. C. Artemisinin kinetics and dynamics during oral and rectal treatment of uncomplicated malaria. Clin. Pharmacol. Ther., 1998, 63 (4), 482-93.
25. Augustijns, P.; D'Hulst, A.; Van Daele, J.; Kinget, R. Transport of artemisinin and sodium artesunate in Caco-2 intestinal epithelial cells. J. Pharm. Sci., 1996, 85 (6), 577-9.
26. Sidhu, J. S.; Ashton, M.; Huong, N. V.; Hai, T. N.; Karlsson, M. O.; Sy, N. D.; Jonsson, E. N.; Cong, L. D. Artemisinin population pharmacokinetics in children and adults with uncomplicated falciparum malaria. Br. J. Clin. Pharmacol., 1998, 45 (4), 347-54.
27. van Agtmael, M. A.; Cheng-Qi, S.; Qing, J. X.; Mull, R.; van Boxtel, C. J. Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria. Int. J. Antimicrob. Agents, 1999, 12 (2), 151-8.
28. Colussi, D.; Parisot, C.; Legay, F.; Lefevre, G. Binding of artemether and lumefantrine to plasma proteins and erythrocytes. Eur. J. Pharm. Sci., 1999, 9 (1), 9-16.
29. Ezzet, F.; Mull, R.; Karbwang, J. Population pharmacokinetics and therapeutic response of CGP 56697 (artemether + benflumetol) in malaria patients. Br. J. Clin. Pharmacol., 1998, 46 (6), 553-61.
30. White, N. J.; van Vugt, M.; Ezzet, F. Clinical pharmacokinetics and pharmacodynamics and pharmacodynamics of artemetherlumefantrine. Clin. Pharmacokinet., 1999, 37 (2), 105-25.
31. Bapiro, T. E.; Sayi, J.; Hasler, J. A.; Jande, M.; Rimoy, G.; Masselle, A.; Masimirembwa, C. M. Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans. Eur. J. Clin. Pharmacol.,2005, 61 (10), 755-61.
32. Svensson, U. S.; Ashton, M. Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br. J. Clin. Pharmacol., 1999, 48 (4), 528-35.
33. Perdaems, N.; Blasco, H.; Vinson, C.; Chenel, M.; Whalley, S.; Cazade, F.; Bouzom, F. Predictions of metabolic drug-drug interactions using physiologically based modelling: Two cytochrome P450 3A4 substrates coadministered with ketoconazole or verapamil. Clin. Pharmacokinet., 2010, 49 (4), 239-58.
34. Kanamitsu, S.; Ito, K.; Sugiyama, Y. Quantitative prediction of in vivo drug-drug interactions from in vitro data based on physiological pharmacokinetics: use of maximum unbound concentration of inhibitor at the inlet to the liver. Pharm. Res., 2000, 17 (3), 336-43.
35. Blanchard, N.; Richert, L.; Coassolo, P.; Lave, T. Qualitative and quantitative assessment of drug-drug interaction potential in man, based on Ki, IC50 and inhibitor concentration. Curr. Drug Metab., 2004, 5 (2), 147-56.
36. Hutagalung, R.; Paiphun, L.; Ashley, E. A.; McGready, R.; Brockman, A.; Thwai, K. L.; Singhasivanon, P.; Jelinek, T.; White, N. J.; Nosten, F. H. A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand. Malaria J., 2005, 4, 46.
37. Ramachandran, G.; Kumar, A. K.; Swaminathan, S.; Venkatesan, P.; Kumaraswami, V.; Greenblatt, D. J. Simple and rapid liquid chromatography method for determination of efavirenz in plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2006, 835 (1-2), 131-5.
38. Rekic, D.; Roshammar, D.; Mukonzo, J.; Ashton, M. In silico prediction of efavirenz and rifampicin drug-drug interaction considering weight and CYP2B6 phenotype. Br. J. Clin. Pharmacol., 2011, 71 (4), 536-43.
39. Woerdenbag, H. J.; Moskal, T. A.; Pras, N.; Malingre, T. M.; El-Feraly, F. S.; Kampinga, H. H.; Konings, A. W. Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J. Nat. Prod., 1993, 56 (6), 849-56.
40. Zheng, G. Q. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med., 1994, 60 (1), 54-7.
41. Lai, H.; Singh, N. P. Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Lett 1995, 91 (1), 41-6.
42. Efferth, T.; Oesch, F. Oxidative stress response of tumor cells: microarray-based comparison between artemisinins and anthracyclines. Biochem. Pharmacol., 2004, 68 (1), 3-10.
43. Efferth, T. Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr. Drug Targets, 2006, 7 (4), 407-21.
44. Efferth, T. Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin--from bench to bedside. Planta medica, 2007, 73 (4), 299-309.
45. Efferth, T.; Kaina, B. Toxicity of the antimalarial artemisinin and its derivatives. Crit. Rev. Toxicol., 2010.
46. Roy, P.; Yu, L. J.; Crespi, C. L.; Waxman, D. J. Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab. Dispos., 1999, 27 (6), 655-66.
47. Nguyen, T. A.; Tychopoulos, M.; Bichat, F.; Zimmermann, C.; Flinois, J. P.; Diry, M.; Ahlberg, E.; Delaforge, M.; Corcos, L.; Beaune, P.; Dansette, P.; Andre, F.; de Waziers, I. Improvement of cyclophosphamide activation by CYP2B6 mutants: from in silico to ex vivo. Mol. Pharmacol., 2008, 73 (4), 1122-33.
48. Lang, T.; Klein, K.; Fischer, J.; Nussler, A. K.; Neuhaus, P.; Hofmann, U.; Eichelbaum, M.; Schwab, M.; Zanger, U. M. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics, 2001, 11 (5), 399-415.