Metabolism of stavudine-5′-[P-bromophenyl methoxyalaninyl phosphate], stampidine, in mice, dogs, and cats

Drug Metabolism and Disposition

Volumn 30, Issue 12, 2002, Pages 1523-1531

  Chen, Chun Lin ^a   Yu, Gengli ^a   Venkatachalam, T K ^a   Uckun, Fatih M ^a  

^a PARKER HUGHES INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 BROMOPHENOL; 4 BROMOPHENYLSULFATE; ALANINYLSTAVUDINE PHOSPHATE; ANTIVIRUS AGENT; CYTOCHROME P450; DRUG METABOLITE; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAMPIDINE; STAVUDINE; STAVUDINE 5' (4 BROMOPHENYLMETHOXYALANINYL PHOSPHATE); SULFOTRANSFERASE; UNCLASSIFIED DRUG; DRUG DERIVATIVE; THYMIDINE PHOSPHATE;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CAT; CONTROLLED STUDY; DOG; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG HYDROLYSIS; DRUG METABOLISM; DRUG SYNTHESIS; DRUG TRANSFORMATION; FEMALE; GUINEA PIG; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; IN VIVO STUDY; LIVER CYTOSOL; LIVER MICROSOME; MALE; MASS SPECTROMETRY; MONKEY; MOUSE; NONHUMAN; PRIORITY JOURNAL; RABBIT; RAT; ANIMAL; CHEMISTRY; COMPARATIVE STUDY; ENZYMOLOGY; INSTITUTE FOR CANCER RESEARCH MOUSE; MACACA; METABOLISM; SPRAGUE DAWLEY RAT;

ANIMALIA; CANIS FAMILIARIS; CAVIA PORCELLUS; FELIS CATUS; HUMAN IMMUNODEFICIENCY VIRUS; ORYCTOLAGUS CUNICULUS; SUS SCROFA;

ANIMALS; CATS; DOGS; GUINEA PIGS; HUMANS; MACACA FASCICULARIS; MICE; MICE, INBRED ICR; MICROSOMES, LIVER; RABBITS; RATS; RATS, SPRAGUE-DAWLEY; STAVUDINE; THYMIDINE MONOPHOSPHATE;

EID: 1842833698     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.30.12.1523     Document Type: Article

References (34)

1. Balzarini J, Karlsson A, Aquaro S, Perno CF, Cahard D, Naesens L, De Clercq E, and McGuigan C (1996a) Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives. Proc Natl Acad Sci USA 93:7295-7299.
2. Balzarini J, Egberink H, Hartmann K, Cahard D, Vahlenkamp T, Thormar H, De Clercq E, and McGuigan C (1996b) Antiretrovirus specificity and intracellular metabolism of 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine) and its 5′-monophosphate triester prodrug So324. Mol Pharmacol 50:1207-1213.
3. Chen CL, Chen H, Zhu DM, and Uckun FM (1999a) Quantitative high-performance liquid chromatography-based detection method for calphostin C, a naturally occurring perylenequinone with potent antileukemic activity. J Chromatogr B Biomed Sci Appl 724:157-162.
4. Chen CL, Levine A, Rao A, O'Neill K, Messinger Y, Myers DE, Goldman F, Hurvitz C, Casper JT, and Uckun FM (1999b) Clinical pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in patients with B-lineage lymphoid malignancies. J Clin Pharmacol 39:1248-1255.
5. Chen CL, Malaviya R, Chen H, Liu XP, and Uckun FM (1999c) Quantitative high-performance liquid chromatographic method for pharmacokinetic studies of the potent mast cell inhibitor 4-(4′-hydroxyphenyl)amino-6,7-dimethoxyquinazoline (WHI-P131). J Chromatogr B Biomed Sci Appl 727:205-212.
6. Chen CL, Malaviya R, Navara C, Chen H, Bechard B, Mitcheltree G, Liu XP, and Uckun FM (1999d) Pharmacokinetics and biologic activity of the novel mast cell inhibitor, 4-(3-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline in mice. Pharm Res 16:117-122.
7. Chen CL, Narla RK, Liu XP, and Uckun FM (1999e) A quantitative HPLC detection method for WHI-P154 [4-(3′-bromo-4′hydroxylphenyl)-amino-6,7-dimethoxyquinazoline]. J Liq Qchromatogr 22:1771-1783.
8. Chen CL, Tai HL, Zhu DM, and Uckun FM (1999f) Pharmacokinetic features and metabolism of calphostin C, a naturally occurring perylenequinone with antileukemic activity. Pharm Res 16:1003-1009.
9. Chen CL and Uckun FM (2000) Highly sensitive liquid chromatography-electrospray mass spectrometry (LC-MS) method for the determination of etoposide levels in human serum and plasma. J Chromatogr B Biomed Sci Appl 744:91-98.
10. Chen CL, Venkatachalam TK, Zhu ZH, and Uckun FM (2001) In vivo pharmacokinetics and metabolism of anti-human immunodeficiency virus agent D4T-5′-[p-bromophenyl methoxyalaninyl phosphate] (SAMPIDINE) in mice. Drug Metab Dispos 29:1035-1041.
11. Coughtrie MW, Gilissen RA, Shek B, Strange RC, Fryer AA, Jones PW, and Bamber DE (1999) Phenol sulphotransferase SULT1A1 polymorphism: Molecular diagnosis and allele frequencies in Caucasian and African populations. Biochem J 337:45-49.
12. Dankovic DA and Billings RE (1985) The role of 4-bromophenol and 4-bromocatechol in bromobenzene covalent binding and toxicity in isolated rat hepatocytes. Toxicol Appl Pharmacol 79:323-331.
13. Duffel MW, Marshal AD, McPhie P, Sharma V, and Jakoby WB (2001) Enzymatic aspects of the phenol (aryl) sulfotransferases. Drug Metab Rev 33:369-395.
14. Egron D, Lefebvre I, Perigaud C, Beltran T, Pompon A, Gosselin G, Aubertin AM, and Imbach JL (1998) Anti-HIV pronucleotides: Decomposition pathways and correlation with biological activities. Bioorg Med Chem Lett 8:1045-1050.
15. Evans WE and Ingelman-Sundberg M (2001) Resequencing the sulfotransferase SULT1 gene provides new insights, while illuminating challenges that lie ahead for pharmacogenomics. Pharmacogenetics 11:745-746.
16. Falany CN (1997) Enzymology of human cytosolic sulfotransferases. FASEB J 11:206-216.
17. Lea AP and Faulds D (1996) Stavudine: A review of its pharmacodynamic and pharmacokinetic properties and clinical potential in HIV infection. Drugs 51:846-864.
18. McGuigan C, Tsang HW, Sutton PW, De Clercq E, and Balzarini J (1998) Synthesis and anti-HIV activity of some novel chain-extended phosphoramidate derivatives of d4T (stavudine): Esterase hydrolysis as a rapid predictive test for antiviral potency. Antiviral Chem Chemother 9:109-115.
19. Monks TJ, Hinson JA, and Gillette JR (1982) Bromobenzene and p-bromophenol toxicity and covalent binding in vivo. Life Sci 30:841-848.
20. Monks TJ, Lau SS, and Higher RJ (1984) Formation of nontoxic reactive metabolites of p-bromophenol. Identification of a new glutathione conjugate. Drug Metab Dispos 12:432-437.
21. Naesens L, Cahard D, Salgado A, Bidois L, De Clercq E, McGuigan C, and Balzarini J (1998) Metabolism and anti-HIV activity of phosphoramidate derivatives of d4T-MP with variations in the amino acid moiety, in Purine and Pyrimidine Metabolism in Man. IX (Griesmacher A, Chiba P, and Muller MM eds) pp 753-757, Plenum Press, New York.
22. Nagata K and Yamazoe Y (2000) Pharmacogenetics of sulfotransferase. Annu Rev Pharmacol Toxicol 40:159-176.
23. Negishi M, Pedersen LG, Petrotchenko E, Shevtsov S, Gorokhov A, Kakuta Y, and Pedersen LC (2001) Structure and function of sulfotransferases. Arch Biochem Biophys 390:149-157.
24. Saboulard D, Naesens L, Cahard D, Salgado A, Pathirana R, Velazquez S, McGuigan C, De Clercq E, and Balzarini (1999) Characterization of the activation pathway of phosphoramidate triester prodrugs of stavudine and zidovudine. Mol Pharmacol 56:693-704.
25. Siddiqui AQ, McGuigan C, Ballatore C, Wedgwood O, De Clercq E, and Balzarini J (1999) Simple mono-derivatisation of the aryl moiety of D4A and DDA-based phosphoramidate prodrugs significantly enhances their anti-HIV potency in cell culture. Bioorg Med Chem Lett 9:2555-2560.
26. Uckun FM, Bellomy K, O'Neill K, Messinger Y, Johnson T, and Chen CL (1999a) Toxicity, biological activity and pharmacokinetics of TXU (anti-CD7)-pokeweed antiviral protein in chimpanzees and adult patients infected with human immunodeficiency virus. J Pharmacol Exp Ther 291:1301-1307.
27. Uckun FM, Chen CL, Lisowski E, Mitcheltree GC, Venkatachalam TK, Erbeck D, Chen H, and Waurzyniak B (2002a) Toxicity and pharmacokinetics of stampidine in mice and rats. Arzn Forsch (in press).
28. Uckun FM, Ek O, Liu XP, and Chen CL (1999b) In vivo toxicity and pharmacokinetic features of the janus kinase 3 inhibitor WHI-P131 [4-(4′hydroxyphenyl)-amino-6,7-dimethoxyquinazoline. Clin Cancer Res 5:2954-2962.
29. Uckun FM, Pendergrass S, Lisowski E, Waurzyniak B, Chen CL, and Venkatachalam TK (2002b) In vivo toxicity, pharmacokinetics and anti-HIV activity of d4T-5′-[p-bromophenyl methoxyalaninyl phosphate] (Stampidine) in mice. Antimicrob Agents Chemother 4:3428-3436.
30. Uckun FM, Pendergrass S, and Venkatachatam TK (2002c) Stampidine is a potent inhibitor of Zidovudine- and NRTI-resistant primary clinical HIV-1 isolates with thymidine analog mutations. Antimicrob Agents Chemother 4:3613-3616.
31. Uckun FM, Thoen J, Chen H, Sudbeck E, Mao C, Malaviya R, Liu XP, and Chen CL (2002d) CYP1A-mediated metabolism of the janus kinase-3 inhibitor 4-(4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline: Structural basis for inactivation by regioselective O-demethylation. Drug Metab Dispos 30:74-85.
32. Uckun FM and Vig R (2000) inventors, Parker Hughes Institute, assignee. Aryl phosphate derivatives of d4T having anti-HIV activity. US patent 6,030,957. 2000 Feb 19.
33. Venkatachalam TK, Tai HL, Vig R, Chen CL, Jan ST, and Uckun FM (1998) Enhancing effects of a mono-bromo substitution at the para position of the phenyl moiety on the metabolism and anti-HIV activity of d4T-phenyl methoxyalaninyl phosphate derivatives. Bioorg Med Chem Lett 8:3121-3126.
34. Vig R, Venkatachalam TK, and Uckun FM (1998) D4T-5′-[p-bromophenyl methoxyalaninyl phosphate] as a potent and non-toxic anti-human immunodeficiency virus agent. Antivir Chem Chemother 9:445-448.