Metabolism of 6-mercaptopurine in the erythrocytes, liver, and kidney of rats during multiple-dose regimens

Cancer Chemotherapy and Pharmacology

Volumn 43, Issue 2, 1999, Pages 133-140

  Innocenti, Federico ^a   Danesi, Romano ^a   Bocci, Guido ^a   Fogli, Stefano ^a   Di Paolo, Antonello ^a   Del Tacca, Mario ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

6 MP; 6 TG; Hydroxyurea; Pharmacokinetics; Rat tissues; Ribavirin

Indexed keywords

HYDROXYUREA; INOSINATE DEHYDROGENASE; MERCAPTOPURINE; RIBAVIRIN; RIBONUCLEOTIDE REDUCTASE; TIOGUANINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BIOTRANSFORMATION; DOSE KIDNEY FUNCTION RELATION; DRUG ERYTHROCYTE LEVEL; DRUG LIVER LEVEL; DRUG METABOLISM; ENZYME INHIBITION; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NONHUMAN; PRIORITY JOURNAL; RAT;

6-MERCAPTOPURINE; ANIMALS; ANTIMETABOLITES; ANTIMETABOLITES, ANTINEOPLASTIC; AREA UNDER CURVE; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; ENZYME INHIBITORS; ERYTHROCYTES; FEMALE; HYDROXYUREA; KIDNEY; LIVER; RATS; RATS, WISTAR; REGRESSION ANALYSIS; RIBAVIRIN;

EID: 0032921838     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s002800050873     Document Type: Article

References (34)

1. Aarbakke J, Janka-Schaub G, Elion GB (1997) Thiopurine biology and pharmacology. Trends Pharmacol Sci 18: 3
2. Bökkerink JPM, Stet EH, De Abreu RA, Damen FJM, Hulscher TW, Bakker MAH, Baal JA van (1992) 6-Mercaptopurine: cytotoxicity and biochemical pharmacology in human malignant T-lymphoblasts. Biochem Pharmacol 45: 1455
3. Bostrom B, Erdmann G (1993) Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia. Am J Pediatr Hematol Oncol 15: 80
4. Chikenji T, Kita K, Tatibana M (1988) Stimulation of de novo biosynthesis of purine and pyrimidine nucleotides in the liver of rats following burn injury. Metabolism 37: 1114
5. Davies HA, Lennard L, Lilleyman JS (1993) Variable mercaptopurine metabolism in children with leukaemia: a problem of non-compliance? Br Med J 306: 1239
6. Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcel Dekker, New York
7. Giverhaugh T, Fuskevaag O-M, Aarbakke J (1997) Methotrexate increases red blood cell concentrations of 6-methylmercaptopurine ribonucleotide in rats in vivo. Cancer Chemother Pharmacol 40: 367
8. Hernandez JS, Van Loon JA, Otterness DM, Guerciolini R. Weinshilbourm RM (1991) Thiopurine methyltransferase regulation in rat kidney: immunoprecipitation studies. Xenobiotica 21: 451
9. Itikura M, Tsuchiya M, Yamashita K (1986) Increase of amidophosphoribosyltransferase activity and phosphoribosyl-pyrophosphate concentration as the basis for increased de novo purine biosynthesis in the regenerating rat liver. Adv Exp Med Biol 195: 347
10. Kato Y, Matushita T, Yokoyama T, Mohri K (1992) Enhanced bioavailability of 6-mercaptopurine after rectal administration in rats. Pharm Res 9: 697
11. Kurowski V, Iven I (1991) Plasma concentrations and organ distribution of thiopurines after oral application of azathioprine in mice. Cancer Chemother Pharmacol 28: 7
12. Lennard L (1992). The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 43: 329
13. Lennard L, Lilleyman JS (1989) Variable 6-mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukaemia. J Clin Oncol 7: 1816
14. Lennard L, Singleton HJ (1992) High-performance liquid chromatographic assay of the methyl and nucleotide metabolites of 6-mercaptopurine: quantitation of red blood cell 6-thioguanine nucleotide, 6-thioinosinic acid and 6-methylmercaptopurine metabolites in single samples. J Chromatogr 583: 83
15. Lennard L, Rees CA, Lilleyman JS, Maddocks JL (1983) Childhood leukaemia: a relationship between intracellular 6-mercaptopurine metabolites and neutropenia. Br J Pharmacol 16: 359
16. Lennard L, Davies HA, Lilleyman JS (1993) Is 6-thioguanine more appropriate than 6-mercaptopurine for children with acute lymphoblastic leukaemia? Br J Cancer 68: 186
17. Liliemark J, Pettersson B, Peterson C (1992) On the biochemical modulation of 6-mercaptopurine by methotrexate in murine WEHI-3b leukemia cells in vitro. Leuk Res 16: 275
18. Lilleyman JS, Lennard L (1994) Mercaptopurine metabolism and risk of relapse in childhood lymphoblastic leukaemia. Lancet 343: 1188
19. Pennington AM, Bronk JR (1995) The absorption of 6-mercaptopurine from 6-mercaptopurine riboside in rat small intestine: effect of phosphate. Cancer Chemother Pharmacol 36: 136
20. Pinkel D (1993) Intravenous mercaptopurine life begins at 40. J Clin Oncol 11: 1826
21. Prajda N, Hata Y, Abonyi M, Singhal RL, Weber G (1993) Sequential impact of tiazofurin and ribavirin on the enzymic program of the bone marrow. Cancer Res 53: 5982
22. Price CJ, Tyl RW, Marks TA, Paschke LL, Ledoux TA, Reel JR (1985) Teratologic and postnatal evaluation of aniline hydrochloride in the Fischer 344 rat. Toxicol Appl Pharmacol 77: 465
23. Ravis WR, Wang JS, Feldman S (1984) Intestinal absorption and metabolism of 6-mercaptopurine in the rat small intestine. Biochem Pharmacol 33: 443
24. Schmiegelow K, Schroder H, Gustafsson G, Kristinsson J, Glomstein A, Salmi T, Wranne L (1995) Risk of relapse in childhood acute lymphoblastic leukemia is related to RBC methotrexate and mercaptopurine metabolites during maintenance chemotherapy. J Clin Oncol 13: 345
25. Schouten TJ, De Abreu RA, Schretlen ED, Vaan GA de, Kleijn E van der (1986) 6-Mercaptopurine: total body autoradiograms and plasma concentration-time curves of 6-MP and metabolites from marmoset monkeys. Pediatr Hematol Oncol 3: 159
26. Sochor M, Kunjara S, Greenbaum AL, McLean P (1989) Changes in pathways of pentose phosphate formation in relation to phosphoribosyl pyrophosphate synthesis in the developing rat kidney. Effects of glucose concentration and electron acceptors. J Dev Physiol 12: 135
27. Spreafico F, Donelli MG, Bossi A, Vecchi A, Standen S, Garattini S, (1973) Immunodepressant activily and 6-mercaptopurine levels after administration of 6-mercaptopurine and azathioprine. Transplantation 16: 269
28. Stet EH, De Abreu RA, Janssen YPG, Bökkerink JPM, Lambooy LHJ, Vogels-Mentink TM, Keizer-Garritsen JJ, Trijbels JMF (1995) Reversal of methylmercaptopurine ribonucleoside cytotoxicity by purine ribonucleosides and adenine. Biochem Pharmacol 49: 49
29. Warren DJ, Andersen A, Slordil L (1995) Quantitation of 6-thioguanine residues in peripheral blood leukocyte DNA obtained from patients receiving 6-mercaptopurine-based maintenance therapy. Cancer Res 55: 1670
30. Weber G, Jayaram HN, Lapis E, Natsumeda Y, Yamada Y, Yamaji Y, Tricot GJ, Hoffman R (1988) Enzyme-pattern-targeted chemotherapy with tiazofurin and allopurinol in human leukemia. Adv Enzyme Regul 27: 405
31. Welch JC, Lilleyman JS (1996) 6-Mercaptopurine dose escalation and its effect on drug tolerance in childhood lymphoblastic leukemia. Cancer Chemother Pharmacol 38: 113
32. Woodson LC, Maus TP, Reiter C, Weinshilboum RM (1981) Rat thiopurine methyltransferase: regulation by testosterone. J Pharmacol Exp Ther 218: 734
33. Yarbro JW (1992) Mechanism of action of hydroxyurea. Semin Oncol 19: 1
34. Zar JH (1984) Biostatistical analysis, 2nd edn. Prentice-Hall, Englewood Cliffs, New Jersey