The combined impact of CYP2C19 and CYP2B6 pharmacogenetics on cyclophosphamide bioactivation

British Journal of Clinical Pharmacology

Volumn 70, Issue 6, 2010, Pages 844-853

  Helsby, Nuala A ^a   Hui, Chung Yee ^a   Goldthorpe, Michael A ^a   Coller, Janet K ^b   Soh, May Ching ^c   Gow, Peter J ^d   De Zoysa, Janak Z ^e   Tingle, Malcolm D ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b UNIVERSITY OF ADELAIDE   (Australia)

^c Waitakere Hospital   (New Zealand)

^d MIDDLEMORE HOSPITAL   (New Zealand)

^e AUCKLAND CITY HOSPITAL   (New Zealand)

Author keywords

Cyclophosphamide; CYP2B6; CYP2C19; Lupus

Indexed keywords

4 HYDROXYCYCLOPHOSPHAMIDE; CARBAMAZEPINE; CITALOPRAM; COTRIMOXAZOLE; CYCLOPHOSPHAMIDE; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; DICLOFENAC; FLUOXETINE; HYDROXYCHLOROQUINE; OMEPRAZOLE; ONDANSETRON; PREDNISONE; THYROXINE;

ADULT; AGED; ALLELE; AREA UNDER THE CURVE; ARTICLE; CAUCASIAN; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG ACTIVATION; DRUG BLOOD LEVEL; DRUG METABOLISM; FEMALE; GENOTYPE; HETEROZYGOSITY; HOMOZYGOTE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LOSS OF FUNCTION MUTATION; LUPUS ERYTHEMATOSUS NEPHRITIS; MALE; PHARMACOGENETICS; PRIORITY JOURNAL; PROTEIN EXPRESSION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADULT; AGED; ALLELES; ARYL HYDROCARBON HYDROXYLASES; CYCLOPHOSPHAMIDE; FEMALE; GENOTYPE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LUPUS NEPHRITIS; MALE; MICROSOMES, LIVER; MIDDLE AGED; OXIDOREDUCTASES, N-DEMETHYLATING; TISSUE BANKS;

EID: 78349270233     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2010.03789.x     Document Type: Article

References (33)

1. Cohen JL, Jao JY. Enzymatic basis of cyclophosphamide activation by hepatic microsomes of the rat. J Pharmacol Exp Ther 1970; 174: 206-10.
2. Chang TKH, Weber GF, Crespi CL, Waxman DJ. Differential activation of cyclophosphamide and ifosfamide by cytochromes P450 2B and 3A in human liver microsomes. Cancer Res 1993; 53: 5629-37.
3. Xie H-J, Yasar U, Lundgren S, Griskevicius L, Terelius Y, Hassan M, Rane A. Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation. Pharmacogenomics J 2003; 3: 53-61.
4. Chen C-H, Lin JT, Goss K, He Y, Halpert JR, Waxman DJ. Activation of the anti-cancer prodrugs cyclophosphamide and ifosfamide: identification of cytochrome P450 2B enzymes and site-specific mutants with improved enzyme kinetics. Mol Pharmacol 2004; 65: 1278-85.
5. Huang Z, Roy P, Waxman DJ. Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzing N-dechloroethylation of cyclophosphamide and ifosfamide. Biochem Pharmacol 2000; 59: 961-72.
6. m catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics 1997; 7: 211-21.
7. Griskevicius L, Yasar U, Sandberg M, Hidestrand M, Eliasson E, Tybring G, Hassan M, Dahl M-L. Bioactivation of cyclophosphamide: the role of polymorphic CYP2C enzymes. Eur J Clin Pharmacol 2003; 59: 103-9.
8. Roy P, Yu LJ, Crespi C, Waxman DJ. Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based in cDNA expressed activities and liver microsomal P450 profiles. Drug Metab Dispos 1999; 2: 655-66.
9. Goldstein JA, Blaisdell J. Genetic tests which identify the principal defects in CYP2C19 responsible for the polymorphism in mephenytoin metabolism. Methods Enzymol 1996; 272: 210-18.
10. Zanger UM, Klein K, Saussele T, Blievernicht J, Hofmann MH, Schwab M. Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics 2007; 8: 743-59.
11. Sim SC, Risinger C, Dahl M-J, Aklillu E, Christensen M, Bertilsson L, Ingelman-Sundberg M. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 2006; 79: 103- 13.
12. Baldwin RM, Ohlsson S, Pedersen RS, Mwinyi J, Ingelman-Sunderg M, Eliasson E, Bertilsson L. Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol 2008; 65: 767-74.
13. Nakajima M, Komagat S, Fujiki Y, Kanada Y, Ebi H, Itoh K, Mukai H, Yokoi T, Minami H. Genetic polymorphisms of CYP 2B6 affect the pharmacokinetics /pharmacodynamics of cyclophosphamide in Japanese cancer patients. Pharmacogenet Genomics 2007; 17: 431-45.
14. Xie H, Griskevicius L, Ståhle L, Hassan Z, Yasar U, Rane A, Broberg U, Kimby E, Hassan M. Pharmacogenetics of cyclophosphamide in patients with hematological malignancies. Eur J Pharm Sci 2006; 27: 54-61.
15. Timm R, Kaiser R, Lotsch J, Heider U, Sezer O, Weisz K, Montemurro M, Roots I, Cascorbi I. Association of cyclophosphamide pharmacokinetics to polymorphic cytochrome P450 2C19. Pharmacogenomics J 2005; 5: 365-73.
16. Ekhart C, Doodeman VD, Rodenhuis S, Smits P, Beijnen JH, Huitema ADR. 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: 515-23.
17. Takada K, Arefayene M, Desta Z, Yarboro CH, Boumpas DT, Balow JE, Flockhart DA, Illei GG. Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis. Arthritis Rheum 2004; 50: 2202-10.
18. Singh G, Saxena N, Aggarwal A, Misra R. Cytochrome P450 polymorphism as a predictor of ovarian toxicity to pulse cyclophosphamide in systemic lupus erythematosus. J Rheumatol 2007; 34: 731-3.
19. Zhou S, Paxton JW, Tingle MD, Kestell P. Identification of the human liver cytochrome P450 isoenzyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5, 6-dimethylxanthenone-4-acetic acid. Drug Metab Dispos 2000; 28: 1449-56.
20. Griskevicius L, Meurling L, Hassan M. Simple method based on fluorescent detection for the determination of 4-hydroxycyclophosphamide in plasma. Ther Drug Monit 2002; 24: 405-9.
21. Takamizawa A, Matsumoto S, Iwata T, Tochino Y, Katagiri K, Yamaguchi K. Studies on cyclophosphamide metabolites and their related compounds. 2. Preparation of an active species of cyclophosphamide and related compounds. J Med Chem 1975; 18: 376-83.
22. Liu J, Kestell P, Findlay M, Riley G, Ackland S, Simpson A, Issacs R, McKeage M. Application of liquid chromatography-mass spectrometry to monitoring plasma cyclophosphamide in phase I trial cancer patients. Clin Exp Pharmacol Physiol 2004; 31: 677-82.
23. Lang T, Klein K, Fischer J, Nussler AK, Neuhaus P, Hofman U, Eichelbaum M, Schwab M, Zanger UM. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 2001; 11: 399-415.
24. Hofmann MH, Blievernicht JK, Klien K, Saussele T, Schaeffeler E, Schwab M, Zanger UM. Aberrant splicing caused by single nucleotide polymorphism c.516G>T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CY2B6 in liver. J Pharmacol Exp Ther 2008; 325: 284-92.
25. Chen T-L, Kennedy MJ, Anderson LW, Kiraly SB, Black KC, Colvin OM, Growchow LB. Non linear pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide in patients with metastatic breast cancer receiving high dose chemotherapy followed by autologous bone marrow transplantation. Drug Metab Dispos 1997; 25: 544-51.
26. Patel M, Clarke AM, Bruce IN, Symmons DPM. The prevalence and incidence of biopsy-proven lupus nephritis in the UK-evidence of an ethnic gradient. Arthritis Rheum 2006; 54: 2963-9.
27. Hart HH, Grigor RR, Caughey DE. Ethnic difference in the prevalence of systemic lupus erythematosus. Ann Rheum Dis 1983; 42: 529-32.
28. Kato M, Chiba K, Horikawa M, Sugiyama Y. The quantitative prediction of in vivo enzyme-induction caused by drug exposure from in vitro information on human hepatocytes. Drug Metab Pharmacokinet 2005; 20: 236-43.
29. Ooe H, Kon J, Oshima H, Mikata T. Thyroid hormone is necessary for expression of constitutive androstane receptor in rat hepatocytes. Drug Metab Dispos 2009; 37: 1963-9.
30. Helsby NA, Lo W-Y, Sharples K, Riley G, Murray M, Spells K, Dzhelai M, Simpson A, Findlay M. CYP2C19 pharmacogenetics in advanced cancer: compromised function independent of genotype. Br J Cancer 2008; 99: 1251-5.
31. Jurima M, Inaba T, Kalow W. Mephenytoin hydroxylase activity in human liver: inhibition by steroids. Drug Metab Dispos 1985; 13: 746-9.
32. Faber OK, Mouridsen HT, Skovsted L. The biotransformation of cyclophosphamide in man: influence of prednisone. Acta Pharmacol Toxicol 1974; 35: 195-200.
33. De Jonge ME, Huitema ADR, Rodenhuis S, Beijnen JH. Clinical pharmacokinetics of cyclophosphamide. Clin Pharmacokinet 2005; 44: 1135-64.