Disposition and oral bioavailability in rats of an antiviral and antitumor amino acid phosphoramidate prodrug of AZT-monophosphate

Pharmaceutical Research

Volumn 20, Issue 3, 2003, Pages 448-451

  Song, Heng ^a,b   Johns, Rachel ^a   Griesgraber, George W ^a   Wagner, Carston R ^a   Zimmerman, Cheryl L ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b IQVIA   (United States)

Author keywords

AZT; Biliary excretion; Intestinal permeability; Oral bioavailability; Pharmacokinetics; Prodrugs; Pronucleotide

Indexed keywords

3' AZIDO 2' DEOXYTHYMIDINE 5' METHYLAMINOTRYPTOPHYLPHOSPHORAMIDE; ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT; PHOSPHORAMIDIC ACID DERIVATIVE; PRODRUG; UNCLASSIFIED DRUG; ZIDOVUDINE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BILIARY EXCRETION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISPOSITION; DRUG EFFECT; DRUG PENETRATION; DRUG UPTAKE; DRUG URINE LEVEL; FEMALE; IN VIVO STUDY; INTESTINE; INTESTINE WALL; NONHUMAN; PH; PRIORITY JOURNAL; RAT; STOMACH ACID; SYSTEMIC CIRCULATION;

ADMINISTRATION, ORAL; ANIMALS; ANTI-HIV AGENTS; ANTINEOPLASTIC AGENTS; BILE; BIOLOGICAL AVAILABILITY; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FEMALE; INTESTINAL ABSORPTION; ORGANOPHOSPHORUS COMPOUNDS; PRODRUGS; RATS; RATS, SPRAGUE-DAWLEY; REVERSE TRANSCRIPTASE INHIBITORS; TIME FACTORS; TISSUE DISTRIBUTION; TRYPTOPHAN; ZIDOVUDINE;

EID: 0037336645     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1022616523678     Document Type: Article

References (16)

1. B. D. Cheson, M. J. Keating, and W. Plunkett. Nucleoside Analogs in Cancer Therapy, Marcel Dekker, New York, 1997.
2. G. A. Balint. Antiretroviral therapeutic possibilities for human immunodeficiency virus/acquired immunodeficiency syndrome. Pharmacol. Ther. 89:17-27 (2001).
3. C. McGuigan, D. Cahard, H. M. Sheeka, E. De Clercq, and J. Balzarini. Aryl phosphoramidate derivatives of d4T have improved anti-HIV efficacy in tissue culture and may act by the generation of a novel intracellular metabolite. J. Med. Chem. 39:1748-1753 (1996).
4. J. Balzarini, A. Karlsson, S. Aquaro, C.-F. Perno, D. Cahard, L. Naesens, E. De Clercq, and C. McGuigan. Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives. Proc. Natl. Acad. Sci. USA 93:7295-7299 (1996).
5. C. R. Wagner, V. I. Iyer, and E. J. McIntee. Pronucleotides: toward the in vivo delivery of antiviral and anticancer nucleotides. Med. Res. Rev. 20:417-451 (2000).
6. G. Antonelli, O. Turriziani, A. Verri, P. Narciso, F. Ferri, G. D'Offizi, and F. Dianzani. Long-term exposure to zidovudine affects in vitro and in vivo the efficiency of phosphorylation of thymidine kinase. AIDS Res. Hum. Retrovirueses 12:223-228 (1996).
7. C. R. Wagner, E. J. McIntee, R. F. Schinazi, and T. W. Abraham. Aromatic amino acid phosphoramidate di- and triester of 3′-azido-3′-deoxythymidine (AZT) are non-toxic inhibitors of HIV-1 replication. Bioorg. Med. Chem. Lett. 5:1819-1824 (1995).
8. S. Chang, G. W. Griesgraber, E. J. McIntee, P. J. Southern, and C. R. Wagner. Amino acid phosphoramidate monoesters of 3′-azido-3′-deoxythymidine: the relationship between antiviral potency and intracellular metabolism. J. Med. Chem. 44:223-231 (2001).
9. V. I. Iyer, G. W. Griesgraber, E. J. McIntee, and C. R. Wagner. Synthesis, in vitro anti-breast cancer activity and intracellular decomposition of amino acid phosphoramidates of AZT. J. Med. Chem. 43:2266-2274 (2000).
10. S.-L. Chang. Ph.D. Thesis: Mechanistic studies of anti-HIV-1 nucleoside phosphoramidates. University of Minnesota, Minneapolis, Minnesota, 1999.
11. H. Song, G. W. Griesgraber, C. R. Wagner, and C. L. Zimmerman. Pharmacokinetics of amino acid phosphoramidate monoesters of AZT in rats. Antimicrob. Agents Chemother. 46:1357-1363 (2002).
12. U.S. Pharmacopeia National Formulary. (USP23-NF18). Rand McNally, Taunton Massachusetts, 1995, p. 2053.
13. Y.K. Pithavala, J. L. Odishaw, S. Han, T. S. Wiedmann, and C. L. Zimmerman. Retinoid absorption from simple and mixed micelles in the rat intestine. J. Pharm. Sci. 84:1360-1365 (1995).
14. H. Song. Ph.D. Thesis: Influence of chemical structure on pharmacokinetics of amino acid phosphoramidate prodrugs of AZT-monophosphate in rats. University of Minnesota, Minneapolis, Minnesota, 2000.
15. S. S. Good and P. de Miranda. Species differences in the metabolism and disposition of antiviral nucleoside analogues: 2. Zidovudine. Antivir. Chem. Chemother. 3:65-77 (1992).
16. H. Han, D. Oh, and G. L. Amidon. Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPEPT1 cells overexpressing a human peptide transporter. Pharm. Res. 15:1382-1386 (1998).