Clinical pharmacokinetics of 3'-azido-3'-deoxythymidine (zidovudine) and catabolites with formation of a toxic catabolite, 3'-amino-3'-deoxythymidine

M. P. Stagg, E. M. Cretton, L. Kidd, Robert B Diasio, J. P. Sommadossi

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Abstract

This study investigated pharmacokinetics and metabolism of 3'-azido-3'-deoxythymidine (zidovudine) in patients after a 1-hour intravenous infusion of 2.5 mg/kg zidovudine with a radiolabeled tracer amount of [5-3H]-zidovudine. In addition to unchanged drug and its 5'-O-glucuronide (zidovudine glucuronide), two novel catabolites of zidovudine were detected as 3'-amino-3'-deoxythymidine (AMT), and its 5'-O-glucuronide (GAMT). The AMT apparent plasma elimination half-life (2.70 ± 0.7 hours) was longer than that of zidovudine (1.20 ± 0.30 hours) and zidovudine glucuronide (1.60 ± 0.5 hours). The zidovudine/AMT plasma peak concentration and area under the concentration-time curve ratios were approximately 8 and 5, respectively. Urinary recovery of radioactivity was essentially complete within 24 hours. AMT glucuronide was not detected in urine or plasma, and only low levels of this catabolite were detected in bile. In contrast, AMT was not detected in bile. The substantial levels of AMT in the plasma of patients after zidovudine administration suggests that this catabolite may affect the pharmacodynamic properties of zidovudine in relation to its activity against human immunodeficiency virus replication and cytotoxicity to host cells.

Original languageEnglish (US)
Pages (from-to)668-676
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume51
Issue number6
StatePublished - 1992
Externally publishedYes

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Zidovudine
Poisons
Pharmacokinetics
Glucuronides
Bile
3'-aminothymidine
Virus Replication
Intravenous Infusions
Radioactivity
Half-Life
HIV
Urine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Clinical pharmacokinetics of 3'-azido-3'-deoxythymidine (zidovudine) and catabolites with formation of a toxic catabolite, 3'-amino-3'-deoxythymidine. / Stagg, M. P.; Cretton, E. M.; Kidd, L.; Diasio, Robert B; Sommadossi, J. P.

In: Clinical Pharmacology and Therapeutics, Vol. 51, No. 6, 1992, p. 668-676.

Research output: Contribution to journalArticle

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