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. 1991 Apr;35(4):747–749. doi: 10.1128/aac.35.4.747

Pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine in rats.

F D Boudinot 1, S G Smith 1, E D Funderburg 1, R F Schinazi 1
PMCID: PMC245090  PMID: 1648888

Abstract

Concentrations of 3'-fluoro-3'-deoxythymidine (FDT) and 3'-deoxy-2',3'-didehydrothymidine (D4T) in plasma declined in a biexponential fashion. Total clearance of D4T (1.75 +/- 0.22 liters/h/kg; mean +/- standard deviation) was significantly greater than that of FDT (1.19 +/- 0.19 liters/h/kg) owing to greater renal and nonrenal clearances of the former. Steady-state volumes of distribution of FDT (1.20 +/- 0.12 liters/kg) and D4T (1.07 +/- 0.15 liters/kg) were similar.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baba M., Pauwels R., Herdewijn P., De Clercq E., Desmyter J., Vandeputte M. Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. Biochem Biophys Res Commun. 1987 Jan 15;142(1):128–134. doi: 10.1016/0006-291x(87)90460-8. [DOI] [PubMed] [Google Scholar]
  2. Balzarini J., Baba M., Pauwels R., Herdewijn P., De Clerq E. Anti-retrovirus activity of 3'-fluoro- and 3'-azido-substituted pyrimidine 2',3'-dideoxynucleoside analogues. Biochem Pharmacol. 1988 Jul 15;37(14):2847–2856. doi: 10.1016/0006-2952(88)90049-4. [DOI] [PubMed] [Google Scholar]
  3. Balzarini J., Kang G. J., Dalal M., Herdewijn P., De Clercq E., Broder S., Johns D. G. The anti-HTLV-III (anti-HIV) and cytotoxic activity of 2',3'-didehydro-2',3'-dideoxyribonucleosides: a comparison with their parental 2',3'-dideoxyribonucleosides. Mol Pharmacol. 1987 Jul;32(1):162–167. [PubMed] [Google Scholar]
  4. Balzarini J., Pauwels R., Herdewijn P., De Clercq E., Cooney D. A., Kang G. J., Dalal M., Johns D. G., Broder S. Potent and selective anti-HTLV-III/LAV activity of 2',3'-dideoxycytidinene, the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine. Biochem Biophys Res Commun. 1986 Oct 30;140(2):735–742. doi: 10.1016/0006-291x(86)90793-x. [DOI] [PubMed] [Google Scholar]
  5. Bazin H., Chattopadhyaya J., Datema R., Ericson A. C., Gilljam G., Johansson N. G., Hansen J., Koshida R., Moelling K., Oberg B. An analysis of the inhibition of replication of HIV and MuLV by some 3'-blocked pyrimidine analogs. Biochem Pharmacol. 1989 Jan 1;38(1):109–119. doi: 10.1016/0006-2952(89)90157-3. [DOI] [PubMed] [Google Scholar]
  6. Boxenbaum H. G., Riegelman S., Elashoff R. M. Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm. 1974 Apr;2(2):123–148. doi: 10.1007/BF01061504. [DOI] [PubMed] [Google Scholar]
  7. Gerlowski L. E., Jain R. K. Physiologically based pharmacokinetic modeling: principles and applications. J Pharm Sci. 1983 Oct;72(10):1103–1127. doi: 10.1002/jps.2600721003. [DOI] [PubMed] [Google Scholar]
  8. Hamamoto Y., Nakashima H., Matsui T., Matsuda A., Ueda T., Yamamoto N. Inhibitory effect of 2',3'-didehydro-2',3'-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus. Antimicrob Agents Chemother. 1987 Jun;31(6):907–910. doi: 10.1128/aac.31.6.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hartmann H., Vogt M. W., Durno A. G., Hirsch M. S., Hunsmann G., Eckstein F. Enhanced in vitro inhibition of HIV-1 replication by 3'-fluoro-3'-deoxythymidine compared to several other nucleoside analogs. AIDS Res Hum Retroviruses. 1988 Dec;4(6):457–466. doi: 10.1089/aid.1988.4.457. [DOI] [PubMed] [Google Scholar]
  10. Herdewijn P., Balzarini J., Baba M., Pauwels R., Van Aerschot A., Janssen G., De Clercq E. Synthesis and anti-HIV activity of different sugar-modified pyrimidine and purine nucleosides. J Med Chem. 1988 Oct;31(10):2040–2048. doi: 10.1021/jm00118a033. [DOI] [PubMed] [Google Scholar]
  11. Kaul S., Dandekar K. A., Pittman K. A. Analytical method for the quantification of 2',3'-didehydro-3'-deoxythymidine, a new anti-human immunodeficiency virus (HIV) agent, by high-performance liquid chromatography (HPLC) and ultraviolet (UV) detection in rat and monkey plasma. Pharm Res. 1989 Oct;6(10):895–899. doi: 10.1023/a:1015972824915. [DOI] [PubMed] [Google Scholar]
  12. Lin T. S., Schinazi R. F., Prusoff W. H. Potent and selective in vitro activity of 3'-deoxythymidin-2'-ene (3'-deoxy-2',3'-didehydrothymidine) against human immunodeficiency virus. Biochem Pharmacol. 1987 Sep 1;36(17):2713–2718. doi: 10.1016/0006-2952(87)90253-x. [DOI] [PubMed] [Google Scholar]
  13. Mansuri M. M., Starrett J. E., Jr, Ghazzouli I., Hitchcock M. J., Sterzycki R. Z., Brankovan V., Lin T. S., August E. M., Prusoff W. H., Sommadossi J. P. 1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine. A highly potent and selective anti-HIV agent. J Med Chem. 1989 Feb;32(2):461–466. doi: 10.1021/jm00122a029. [DOI] [PubMed] [Google Scholar]
  14. Patel B. A., Chu C. K., Boudinot F. D. Pharmacokinetics and saturable renal tubular secretion of zidovudine in rats. J Pharm Sci. 1989 Jul;78(7):530–534. doi: 10.1002/jps.2600780704. [DOI] [PubMed] [Google Scholar]
  15. Schinazi R. F., Boudinot F. D., Doshi K. J., McClure H. M. Pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine in rhesus monkeys. Antimicrob Agents Chemother. 1990 Jun;34(6):1214–1219. doi: 10.1128/aac.34.6.1214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Unadkat J. D., Wang J. P., Pulham D., Semmes R. L. Dose-ranging pharmacokinetics of zidovudine (azidothymidine) in the rat. Pharm Res. 1989 Aug;6(8):734–736. doi: 10.1023/a:1015954926307. [DOI] [PubMed] [Google Scholar]

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