3′-Azido-2′,3′-Dideoxyuridine (AzddU): Comparative Pharmacokinetics with 3′-Azido-3′-Deoxythymidine (AZT) in Monkeys

F. Douglas Boudinot, James M. Gallo, Kokila J. Doshi, Raymond F. Schinazi, Harold M. Mcclure, Daniel C. Anderson, Pullaiah C. Kambhampathi, Chung K. Chu

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32 Scopus citations

Abstract

The pharmacokinetics of the anti-human immunodeficiency virus type 1 nucleosides, 3′-azido-2′,3′-dideoxyuridine (AzddU) and 3′-azido-3′-deoxythymidine (AZT) were characterized in rhesus monkeys. Half-life, total clearance, and steady-state volume of distribution were similar for both compounds. The observed pharmacokinetic parameters for AZT were comparable to those previously reported in humans. Oral absorption of AzddU and AZT was virtually complete after 60 mg/kg. However, bioavailability of both nucleosides was markedly lower (<50%) after 200 mg/kg, possibly indicating the involvement of a saturable absorption mechanism. The nucleosides were also well absorbed after subcutaneous administration. AzddU and AZT penetrated the cerebrospinal fluid (CSF) with concentration ratios in CSF:serum ranging from 0.05 to 0.25 one hour after drug administration. The glucuronides of AZT and AzddU were readily detected in urine. Hemogram and blood chemistry values for animals receiving short-term treatment (3 doses) with either AZT or AzddU did not exhibit any significant changes when compared with untreated control monkeys. The similar pharmacokinetic characteristics of AzddU compared with AZT suggest that clinical trials of AzddU are warranted.

Original languageEnglish
Pages (from-to)219-228
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume6
Issue number2
DOIs
StatePublished - Feb 1990
Externally publishedYes

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