Bioactivation of capecitabine in human liver: Involvement of the cytosolic enzyme on 5′-deoxy-5-fluorocytidine formation

Drug Metabolism and Disposition

Volumn 32, Issue 7, 2004, Pages 762-767

  Tabata, Toshiki ^a   Katoh, Miki ^a   Tokudome, Shogo ^b   Hosakawa, Masakiyo ^c   Chiba, Kan ^c   Nakajima, Miki ^a   Yokoi, Tsuyoshi ^a  

^a KANAZAWA UNIVERSITY   (Japan)

^b DOKKYO MEDICAL UNIVERSITY   (Japan)

^c CHIBA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO 2,4 DIHYDROXYPYRIDINE; 5' DEOXY 5 FLUOROCYTIDINE; CAPECITABINE; CARBOXYLESTERASE; CYTIDINE DEAMINASE; DIHYDROPYRIMIDINE DEHYDROGENASE; DOXIFLURIDINE; DRUG METABOLITE; FLUOROURACIL; THYMIDINE PHOSPHORYLASE; UNCLASSIFIED DRUG;

ARTICLE; BIOTRANSFORMATION; CATALYSIS; CONTROLLED STUDY; DRUG ACTIVITY; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG TRANSFORMATION; ENZYME ACTIVITY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; LIVER CYTOSOL; LIVER MICROSOME; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANTIMETABOLITES, ANTINEOPLASTIC; CYTOSOL; DEOXYCYTIDINE; DIHYDROURACIL DEHYDROGENASE (NADP); FLOXURIDINE; FLUOROURACIL; HUMANS; MICROSOMES, LIVER; PRODRUGS; PYRIDINES; THYMIDINE PHOSPHORYLASE;

EID: 3042544338     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.32.7.762     Document Type: Article

References (28)

1. Brandt E, Heymann E, and Mentlein R (1980) Selective inhibition of rat liver carboxylesterases by various organophosphorus diesters in vivo and in vitro. Biochem Pharmacol 29:1927-1931.
2. Camiener GW and Smith CG (1965) Studies of the enzymatic deamination of cytosine arabinoside. 1. Enzyme distribution and species specificity. Biochem Pharmacol 14:1405-1416.
3. Fukushima M, Suzuki N, Emura T, Yano S, Kazuno H, Tada Y, Yamada Y, and Asao T (2000) Structure and activity of specific inhibitors of thymidine phosphorylase to potentiate the function of antitumor 2′- deoxyribonucleosides. Biochem Pharmacol 59:1227-1236.
4. Furihata M, Hosokawa M, Nakata F, Satoh T, and Chiba K (2003) Purification, molecular cloning and functional expression of C57BL/6 inducible mouse liver acylcamitine hydrolase, belonging to the carboxylesterase multigene family. Arch Biochem Biophys 416:101-109.
5. Harris BE, Song RL, He YJ, Soong SJ, and Diasio RB (1998) Circadian rhythm of rat liver dihydropyrimidine dehydrogenase. Possible relevance to fluoropyrimidine chemotherapy. Biochem Pharmacol 37:4759-4762.
6. Hosokawa M, Endo T, Fujisawa M, Hara S, Iwata N, Sato Y, and Satoh T (1995) Interindividual variation in carboxylesterase levels in human liver microsomes. Drug Metab Dispos 23:1022-1027.
7. Inoue M, Morikawa M, Tsuboi M, Yamada T, and Sugiura M (1979) Hydrolysis of ester-type drugs by the purified esterase from human intestinal mucosa. Jpn J Pharmacol 29:17-25.
8. Ishikawa T, Sekiguchi F, Fukase Y, Sawada N, and Ishitsuka H (1998a) Positive correlation between the efficacy of capecitabine and doxifluridine and the ratio of thymidine phosphorylase to dihydropyrimidine dehydrogenase activities in tumors in human cancer xenografts. Cancer Res 58:685-690.
9. Ishikawa T, Utoh M, Sawada N, Nishida M, Fukase Y, Sekiguchi F, and Ishitsuka H (1998b) Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem Pharmacol 55:1091-1097.
10. Junge W, Heymann E, Krisch K, and Hollandt H (1974) Human liver carboxylesterase. Purification and molecular properties. Arch Biochem Biophys 165:749-763.
11. Kirch HC, Schroder J, Hoppe H, Esche H, Seeber S, and Schutte J (1998) Recombinant gene products of two natural variants of the human cytidine deaminase gene confer different deamination rates of cytarabine in vitro. Exp Hematol 26:421-425.
12. Kono A, Hara Y, and Matsushima Y (1981) Enzymatic formation of 5-fluorouracil from l-(tetrahydro-2-furanyl)-5-fluorouracil (tegafur) in human tumor tissues. Chem Pharm Bull 29:1486-1488.
13. Lowry OH, Rosebrough NJ, Farr AL, and Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265-275.
14. Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, and Ishitsuka H (1998) Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in turnouts by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 34:1274-1281.
15. Mori K, Hasegawa M, Nishida M, Toma H, Fukuda M, Kubota T, Nagasue N, Yamana H, Chung K, Ikeda T, et al. (2000) Expression levels of thymidine phosphorylase and dihydropyrimidine dehydrogenase in various human tumor tissues. Int J Oncol 17:33-38.
16. Ninomiya Y, Miwa M, Eda H, Sahara H, Fujimoto K, Ishida M, Umeda I, Yokose K, and Ishitsuka H (1990) Comparative antitumor activity and intestinal toxicity of 5′-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl- 5′-deoxy-5-fluorocytidine. Jpn J Cancer Res 81:188-195.
17. Nishida M, Hino A, Mori K, Matsumoto T, Yoshikubo T, and Ishitsuka H (1996) Preparation of anti-human thymidine phosphorylase monoclonal antibodies useful for detecting the enzyme levels in tumor tissues. Biol Pharm Bull 19:1407-1411.
18. Ohta Y, Sueki K, Kitta K, Takemoto K, Ishitsuka H, and Yagi Y (1980) Comparative studies on the immunosuppressive effect among 5′-deoxy-5- fluorouridine, ftorafur and 5-fluorouracil. Gann 71:190-196.
19. Satoh T and Hosokawa M (1995) Molecular aspects of carboxylesterase isoforms in comparison with other esterases. Toxicol Lett 82:439-445.
20. Satoh T and Hosokawa M (1998) The mammalian carboxylesterases: from molecules to functions. Annu Rev Pharmacol Toxicol 38:257-288.
21. Schüller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, and Reigner B (2000) Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 45:291-297.
22. Shimma N, Umeda I, Arasaki M, Murasaki C, Masubuchi K, Kohchi Y, Miwa M, Ura M, Sawada N, Tahara H, et al. (2000) The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine. Bioorg Med Chem 8:1697-1706.
23. Tatsumi K, Fukushima M, Shiŕsaka T, and Fujii S (1987) Inhibitory effects of pyrimidine, barbituric acid and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res 78:748-755.
24. Wentworth DF and Wolfenden R (1975) On the interaction of 3,4,5,6-tetrahydrouridine with human liver cytidine deaminase. Biochemistry 14:5099-5105.
25. Xu G, Zhang W, Ma MK, and McLeod HL (2002) Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan. Clin Cancer Res 8:2605-2611.
26. Yamazaki H, Shibata A, Suzuki M, Nakajima M, Shimada N, Guengerich FP, and Yokoi T (1999) Oxidation of troglitazone to a quinone type metabolite catalyzed by cytochrome P450 2C8 and P450 3A4 in human liver microsomes. Drug Metab Dispos 27:1260-1266.
27. Yoshimura A, Kuwazuru Y, Furukawa T, Yoshida H, Yamada K, and Akiyama S (1990) Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors. Biochim Biophys Acta 1034:107-113.
28. Yue L, Saikawa Y, Ota K, Tanaka M, Nishimura R, Uehara T, Maeba H, Ito T, Sasaki T, and Koizumi S (2003) A functional single-nucleotide polymorphism in the human cytidine deaminase gene contributing to ara-C sensitivity. Pharmacogenetics 13:29-38.