In vitro hepatic metabolism of cediranib, a potent vascular endothelial growth factor tyrosine kinase inhibitor: Interspecies comparison and human enzymology

Drug Metabolism and Disposition

Volumn 38, Issue 10, 2010, Pages 1688-1697

  Schulz Utermoehl, Timothy ^a   Spear, Michael ^a   Pollard, Christopher R J ^a   Pattison, Christine ^a   Rollison, Helen ^a   Sarda, Sunil ^a   Ward, Michelle ^a   Bushby, Nick ^a   Jordan, Angela ^a   Harrison, Mike ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 AMINOBENZOTRIAZOLE; CEDIRANIB; CYTOCHROME P450; DRUG METABOLITE; GLUCURONIDE; GLUCURONOSYLTRANSFERASE 1A4; PYRROLIDINE DERIVATIVE;

ANIMAL CELL; ARTICLE; CELL CULTURE; CLINICAL EVALUATION; COMPARATIVE STUDY; DOG; DRUG DISPOSITION; DRUG METABOLISM; ENZYMOLOGY; GLUCURONIDATION; GUINEA PIG; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER CELL; LIVER CELL CULTURE; LIVER METABOLISM; LIVER MICROSOME; METABOLITE; MONKEY; MOUSE; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RAT; RECURRENT CANCER; SPECIES DIVERSITY;

ADULT; ANIMALS; CELLS, CULTURED; CYTOCHROME P-450 ENZYME SYSTEM; DOGS; FEMALE; GLUCURONOSYLTRANSFERASE; GUINEA PIGS; HEPATOCYTES; HUMANS; LIVER; MACACA FASCICULARIS; MACACA MULATTA; MALE; METABOLIC DETOXICATION, PHASE I; METABOLIC DETOXICATION, PHASE II; MICE; MICROSOMES, LIVER; MIDDLE AGED; OXYGENASES; QUINAZOLINES; RABBITS; RATS; RATS, WISTAR; RECEPTOR PROTEIN-TYROSINE KINASES; SPECIES SPECIFICITY; SWINE; SWINE, MINIATURE; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

CANIS FAMILIARIS; CAVIA; MACACA FASCICULARIS; MACACA MULATTA; ORYCTOLAGUS CUNICULUS; RATTUS; RATTUS NORVEGICUS; SUIDAE;

EID: 77957147572     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.110.033159     Document Type: Article

References (28)

1. Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, et al. (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83-95.
2. Beedham C (2001) Molybdenum hydroxylases, in Enzyme Systems That Metabolise Drugs and Other Xenobiotics (Ioannides C ed) John Wiley & Sons Ltd., London.
3. Benoit-Biancamano MO, Adam JP, Bernard O, Court MH, Leblanc MH, Caron P, and Guillemette (2009) A pharmacogenetics study of the human glucuronosyltransferase UGT1A4. Pharmacogenet Genom 19:945-954.
4. Cashman JR (1995) Structural and catalytic properties of the mammalian flavin-containing monooxygenase. Chem Res Tox 8:166-181.
5. Cashman JR and Zhang J (2006) Human flavin-containing monooxygenases. Annu Rev Pharmacol Toxicol 46:65-100.
6. Chaudhuri NK, Servando OA, Manniello MJ, Luders RC, Chao DK, and Bartlett MF (1976) Metabolism of tripelennamine in man. Drug Metab Dispos 4:372-378.
7. Chen E, Jonker D, Gauthier I, MacLean M, Wells J, Powers J, and Seymour L (2009) Phase I study of cediranib in combination with oxaliplatin and infusional 5-fluorouracil in patients with advanced colorectal cancer. Clin Cancer Res 15:1481-1486.
8. Chiu SH and Huskey SW (1998) Species differences in N-glucuronidation. Drug Metab Dispos 26:838-847.
9. Delbressine LP, Moonen ME, Kaspersen FM, Jacobs PL, and Wagenaars GL (1992) Biotransformation of mianserin in laboratory animals and man. Xenobiotica 22:227-336.
10. Drevs J, Siegert P, Medinger M, Mross K, Strecker R, Zirrgiebel U, Harder J, Blum H, Robertson J, Jürgensmeier JM, et al. (2007) Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 25:3045-3054. (Pubitemid 47218051)
11. Ehmer U, Vogel A, Schütte JK, Krone B, Manns MP, and Strassburg CP (2004) Variation of hepatic glucuronidation: novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4. Hepatology 39:970-977. (Pubitemid 38428936)
12. Fischer LJ, Thies RL, Charkowski D, and Donham KJ (1980) Formation and urinary excretion of cyproheptadine glucuronide in monkeys, chimpanzees, and humans. Drug Metab Dispos 8:422-424. (Pubitemid 11210391)
13. Green MD, Bishop WP, and Tephly TR (1995) Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium-linked glucuronides. Drug Metab Dispos 23:299-302.
14. Green MD and Tephly TR (1996) Glucuronidation of amines and hydroxylated xenobiotics and endobiotics catalyzed by expressed human UGT1.4 protein. Drug Metab Dispos 24:356-363.
15. Green MD and Tephly TR (1998) Glucuronidation of amine substrates by purified and expressed UDP-glucuronosyltransferase proteins. Drug Metab Dispos 26:860-867.
16. Kiang TK, Ensom MH, and Chang TK (2005) UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther 106:97-132.
17. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, and Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841-844. (Pubitemid 23132159)
18. Kubota T, Lewis BC, Elliot DJ, Mackenzie PI, and Miners JO (2007) Critical roles of residues 36 and 40 in the phenol and tertiary amine aglycone substrate selectivities of UDP-glucuronosyltransferases 1A3 and 1A4. Mol Pharmacol 72:1054-1062. (Pubitemid 47481428)
19. LeCluyse E, Madan A, Hamilton G, Carroll K, DeHaan R, and Parkinson A (2000) Expression and regulation of cytochrome P450 enzymes in primary cultures of human hepatocytes. J Biochem Mol Toxicol 14:177-188.
20. Lang D and Kalgutkar AS (2003) Non-P450 mediated oxidative metabolism of xenobiotics, in Drug Metabolizing Enzymes: Cytochrome P450 and Other Enzymes in Drug Discovery and Development (Lee JS, Obach RS, and Fisher MB eds) pp 483-540, FontisMedia SA, Lausanne, Switzerland.
21. +-glucuronide metabolite of cediranib. J Pharm Biomed Anal 53:526-536.
22. Miners JO, Smith PA, Sorich MJ, McKinnon RA, and Mackenzie PI (2004) Predicting human drug glucuronidation parameters: application of in vitro and in silico modeling approaches. Annu Rev Pharmacol Toxicol 44:1-25.
23. Mitchell SC (2008) Flavin mono-oxygenase (FMO) - the 'other' oxidase. Curr Drug Metab 9:280-284.
24. Mori A, Maruo Y, Iwai M, Sato H, and Takeuchi Y (2005) UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation. Drug Metab Dispos 33:672-675. (Pubitemid 40593882)
25. Saeki M, Saito Y, Jinno H, Sai K, Hachisuka A, Kaniwa N, Ozawa S, Kawamoto M, Kamatani N, Shirao K, et al. (2005) Genetic variations and haplotypes of UGT1A4 in a Japanese population. Drug Metab Pharmacokinet 20:144-151.
26. Uchaipichat V, Mackenzie PI, Elliot DJ, and Miners JO (2006) Selectivity of substrate (trifluoperazine) and inhibitor (amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone) "probes" for human UDP-glucuronosyltransferases. Drug Metab Dispos 34:449-456.
27. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, et al. (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 65:4389-4400.
28. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, and Ball SE (2004) Drug-drug interactions for UDP- glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 32:1201-1208. (Pubitemid 39410902)