Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice

Cancer Chemotherapy and Pharmacology

Volumn 67, Issue 2, 2011, Pages 421-430

  Beumer, Jan H ^a,b   Eiseman, Julie L ^a,c   Gilbert, Judith A ^d   Holleran, Julianne L ^a   Yellow Duke, Archibong E ^a   Clausen, Dana M ^a   D'Argenio, David Z ^e   Ames, Matthew M ^d   Hershberger, Pamela A ^a,c   Parise, Robert A ^b   Bai, Lihua ^a,c   Covey, Joseph M ^f   Egorin, Merrill J ^a,c  

^a UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d MAYO GRADUATE SCHOOL   (United States)

^e University of Southern California   (United States)

^f NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Bioavailability; Cytidine deaminase; Metabolism; Mouse; Tetrahydrouridine; THU

Indexed keywords

CYTIDINE DEAMINASE; PRODRUG; TETRAHYDROURIDINE; TRIACETYL 3,4,5,6 TETRAHYDROURIDINE; UNCLASSIFIED DRUG; ANTINEOPLASTIC ANTIMETABOLITE; DEOXYCYTIDINE; DRUG DERIVATIVE; GEMCITABINE; RECOMBINANT PROTEIN; TRIACETYL-3,4,5,6-TETRAHYDROURIDINE;

ACETYLATION; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG URINE LEVEL; HYDROLYSIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; BIOAVAILABILITY; BIOCATALYSIS; BIOLOGICAL MODEL; BLOOD; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; GENETICS; GERMFREE ANIMAL; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MALE; METABOLISM; MOUSE STRAIN; ORAL DRUG ADMINISTRATION; URINE;

ADMINISTRATION, ORAL; ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; AREA UNDER CURVE; BIOCATALYSIS; BIOLOGICAL AVAILABILITY; BLOOD; CYTIDINE DEAMINASE; DEOXYCYTIDINE; HUMANS; INJECTIONS, INTRAVENOUS; MALE; MICE; MICE, INBRED STRAINS; MODELS, BIOLOGICAL; PRODRUGS; RECOMBINANT PROTEINS; SPECIFIC PATHOGEN-FREE ORGANISMS; TETRAHYDROURIDINE; URINE;

EID: 79953749077     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00280-010-1337-6     Document Type: Article

References (39)

1. Akaike H (1979) A Bayesian extension of the minimal AIC procedures of autoregressive model fitting. Biometrika 66:237-242 (Pubitemid 9228573)
2. Ashour OM, Naguib FN, el Kouni MH (1996) 5-(m-Benzyloxy-benzyl) barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2′, 3′, 5′-tri-O-acetyluridine, a prodrug of uridine, as modulators of plasma uridine concentration. Implications for chemotherapy. Biochem Pharmacol 51:1601-1611
3. Beumer JH, Eiseman JL, Parise RA, Florian JA Jr, Joseph E, D'Argenio DZ, Parker RS, Kay B, Covey JM, Egorin MJ (2008) Plasma pharmacokinetics and oral bioavailability of 3, 4, 5, 6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice. Cancer Chemother Pharmacol 62:457-464
4. Beumer JH, Eiseman JL, Parise RA, Joseph E, Covey JM, Egorin MJ (2008) Modulation of gemcitabine (2′, 2′-difiuoro-2′-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3, 4, 5, 6-tetrahydrouridine. Clin Cancer Res 14:3529-3535
5. Beumer JH, Eiseman JL, Parise RA, Joseph E, Holleran JL, Covey JM, Egorin MJ (2006) Pharmacokinetics, metabolism, and oral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine in mice. Clin Cancer Res 12:7483-7491 (Pubitemid 46095424)
6. Beumer JH, Parise RA, Newman EM, Doroshow JH, Synold TW, Lenz HJ, Egorin MJ (2008) Concentrations of the DNA methyltransferase inhibitor 5-fluoro-2′-deoxycytidine (FdCyd) and its cytotoxic metabolites in plasma of patients treated with FdCyd and tetrahydrouridine (THU). Cancer Chemother Pharmacol 62:363-368 (Pubitemid 351692084)
7. Creasey WA, Fink ME, Handschumacher RE, Calabresi P (1963) Clinical and pharmacological studies with 2′, 3′, 5′-triacetyl-6- azauridine. Cancer Res 23:444-453
8. D'Argenio DZ, Schumitzky A, Wang X (2009) ADAPT 5 user's guide: pharmacokinetic/pharmacodynamic systems analysis software. Biomedical Simulations Resource, Los Angeles
9. Dareer SM, Mulligan LT Jr, White V, Tillery K, Mellett LB, Hill DL (1977) Distribution of [3H]cytosine arabinoside and its products in mice, dogs, and monkeys and effect of tetrahydrouridine. Cancer Treat Rep 61:395-407 (Pubitemid 8137942)
10. Doolittle CH, McDonald CJ, Calabresi P (1977) Pharmacological studies of neurotoxicity in patients with psoriasis treated with azaribine, utilizing high-pressure liquid chromatography. J Lab Clin Med 90:773-785 (Pubitemid 8216199)
11. Doroshow JH, McCoy S, Macdonald JS, Issell BF, Patel T, Cobb PW, Yost KJ, Abbruzzese JL (2006) Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a southwest oncology group study. Invest New Drugs 24:537-542 (Pubitemid 44273030)
12. BRENDA The Comprehensive Enzyme Information System. http://wwwbrendauni- koelnde/indexphp4 (2007) Available at http://www.brenda.uni-koeln.de/index.php4 (1/Feb./2007)
13. el Dareer SM, White V, Chen FP, Mellett LB, Hill DL (1976) Distribution of tetrahydrouridine in experimental animals. Cancer Treat Rep 60:1627-1631 (Pubitemid 8059961)
14. Ellison G, Straumfjord JV Jr, Hummel JP (1958) Buffer capacities of human blood and plasma. Clin Chem 4:452-461
15. Fenaux P (2005) Inhibitors of DNA methylation: beyond myelodysplastic syndromes. Nat Clin Pract Oncol 2 (Suppl 1): S36-S44 (Pubitemid 43135233)
16. Gilbert JA, Salavaggione OE, Ji Y, Pelleymounter LL, Eckloff BW, Wieben ED, Ames MM, Weinshilboum RM (2006) Gemcitabine pharmacogenomics: cytidine deaminase and deoxycytidylate deaminase gene resequencing and functional genomics. Clin Cancer Res 12:1794-1803
17. Greer S, Schwade J, Marion HS (1995) Five-chlorodeoxycytidine and biomodulators of its metabolism result in fifty to eighty percent cures of advanced EMT-6 tumors when used with fractionated radiation. Int J Radiat Oncol Biol Phys 32:1059-1069
18. Hale JT, Bigelow JC, Mathews LA, McCormack JJ (2002) Analytical and pharmacokinetic studies with 5-chloro-2′-deoxycytidine. Biochem Pharmacol 64:1493-1502
19. Handschumacher RE, Creasey WA, Fink ME, Calabresi P, Welch AD (1962) Pharmacological and clinical studies with triacetyl 6-azauridine. Cancer Chemother Rep 16:267-269
20. Hidalgo M, Villalona-Calero MA, Eckhardt SG, Drengler RL, Rodriguez G, Hammond LA, Diab SG, Weiss G, Garner AM, Campbell E, Davidson K, Louie A, O'Neil JD, von Borstel R, Von Hoff DD, Rowinsky EK (2000) Phase I and pharmacologic study of PN401 and fiuorouracil in patients with advanced solid malignancies. J Clin Oncol 18:167-177 (Pubitemid 30036350)
21. Ho DH, Bodey GP, Hall SW, Benjamin RS, Brown NS, Freireich EJ, Loo TL (1978) Clinical pharmacology of tetrahydrouridine. J Clin Pharmacol 18:259-265 (Pubitemid 8384293)
22. Kaye SB (1998) New antimetabolites in cancer chemotherapy and their clinical impact. Br J Cancer 78 (Suppl 3):1-7 (Pubitemid 128710590)
23. Klubes P, Geffen DB, Cysyk RL (1986) Comparison of the bioavailability of uridine in mice after either oral or parenteral administration. Cancer Chemother Pharmacol 17:236-240 (Pubitemid 16070932)
24. Kreis W, Chan K, Budman DR, Schulman P, Allen S, Weiselberg L, Lichtman S, Henderson V, Freeman J, Deere M (1988) Effect of tetrahydrouridine on the clinical pharmacology of 1-beta-D-arabinofuranosylcytosine when both drugs are coinfused over three hours. Cancer Res 48:1337-1342 (Pubitemid 18075555)
25. Kreis W, Woodcock TM, Gordon CS, Krakoff IH (1977) Tetrahydrouridine: physiologic disposition and effect upon deamination of cytosine arabinoside in man. Cancer Treat Rep 61:1347-1353 (Pubitemid 8204105)
26. Lyko F, Brown R (2005) DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J Natl Cancer Inst 97:1498-1506 (Pubitemid 41631949)
27. Marsh JH, Kreis W, Barile B, Akerman S, Schulman P, Allen SL, DeMarco LC, Schuster MW, Budman DR (1993) Therapy of refractory/relapsed acute myeloid leukemia and blast crisis of chronic myeloid leukemia with the combination of cytosine arabinoside, tetrahydrouridine, and carboplatin. Cancer Chemother Pharmacol 31:481-484 (Pubitemid 23093321)
28. Mekras JA, Boothman DA, Greer SB (1985) Use of 5- trifiuoromethyldeoxycytidine and tetrahydrouridine to circumvent catabolism and exploit high levels of cytidine deaminase in tumors to achieve DNA-and target-directed therapies. Cancer Res 45:5270-5280 (Pubitemid 16200832)
29. Neil GL, Moxley TE, Kuentzel SL, Manak RC, Hanka LJ (1975) Enhancement by tetrahydrouridine (NSC-112907) of the oral activity of 5-azacytidine (NSC-102816) in L1210 leukemic mice. Cancer Chemother Rep 59:459-465
30. Neil GL, Moxley TE, Manak RC (1970) Enhancement by tetrahydrouridine of 1-beta-D-arabinofuranosylcytosine (cytarabine) oral activity in L1210 leukemic mice. Cancer Res 30:2166-2172
31. Newman EM, Longmate J, Lenz H, Carroll M, Stalter S, Lim D, Raschko D, Shibata S, Somlo G, Doroshow J (2002) Phase I and clinical pharmacokinetic evaluation of the DNA methyltransferase inhibitor 5-fluoro-2′- deoxycytidine: a California Cancer Consortium study. Proceedings of the American Society of Clinical Oncology 21:108a
32. Parise RA, Egorin MJ, Eiseman JL, Joseph E, Covey JM, Beumer JH (2007) Quantitative determination of the cytidine deaminase inhibitor tetrahydrouridine (THU) in mouse plasma by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 21:1991-1997 (Pubitemid 46999249)
33. Saif MW, von Borstel R (2006) 5-Fluorouracil dose escalation enabled with PN401 (triacetyluridine): toxicity reduction and increased antitumor activity in mice. Cancer Chemother Pharmacol 58:136-142
34. Guidance for Industry-Bioanalytical Method Validation (2007)
35. http://www.fda.gov/cder/guidance/index.htm. Accessed May 2001.
36. http://www.fda.gov/cder/guidance/index.htm. Accessed 1 Feb. 2007
37. van Groeningen CJ, Peters GJ, Nadal JC, Laurensse E, Pinedo HM (1991) Clinical and pharmacologic study of orally administered uridine. J Natl Cancer Inst 83:437-441
38. von Borstel R, O'Neil J, Bamat M (2009) Vistonuridine: an orally administered, life-saving antidote for 5-fiuorouracil (5FU) overdose. Proc Am Soc Clin Oncol 27:15s
39. Wong PP, Currie VE, Mackey RW, Krakoff IH, Tan CT, Burchenal JH, Young CW (1979) Phase I evaluation of tetrahydrouridine combined with cytosine arabinoside. Cancer Treat Rep 63:1245-1249 (Pubitemid 10187965)