Pharmacokinetics of tiazofurin in dogs

✍ Scribed by E. K. Obeng; J. J. Vallner; D. E. Cadwallader; Dr R. L. Tackett

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 332 KB
• Volume: 8
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510080204

✦ Synopsis

The pharmacokinetics of total and free tiazofurin, an antineoplastic agent, was studied in healthy mongrel dogs following intravenous and oral administration of the drug. The free fraction of tiazofurin was obtained from plasma by an ultrafiltration technique using a micropartition system. Total and free tiazofurin levels were determined by a sensitive high performance liquid chromatographic method. The percentage of tiazofurin bound to plasma proteins remained constant at approximately 15 per cent following administration to healthy mongrel dogs. The mean pharmacokinetic parameters of elimination rate constant ( K ) , effective half-life (t%), mean residence time (MRT) and the time to reach peak plasma level (&,,-after oral administration) were 0.32 -t 0.04 h-', 2.24 rf: 0.25 h, 3.23 -t 0.36 h, and 1.78 k 0.50 h, respectively. The apparent volume of distribution at steady state was 0.98 k 0.30 1 kg-l and the plasma clearance was 5.24 f 2.39 ml min-l kg-I. About 90 per cent of tiazofurin was absorbed folowing oral administration. The pharmacokinetic parameters did not differ significantly between the total and free drug levels, indicating that the pharmacokinetics of total tiazofurin levels reflect those of the free tiazofurin in plasma.

KEY WORDS Tiazofurin Pharmacokinetics Non-compartmental analysis Free drug level

nucleoside whose synthesis was reported by Fuertes et al. and by Srivastava et ~1 . ~ It is a structural analogue of ribavirin, a potent antiviral agent."' Tiazofurin possesses relatively poor antiviral properties but exhibits excellent anti-tumor activity including curative activity against Lewis lung c a r ~i n o m a . ~ Srivastava et ~1 . ~ reported that tiazofurin specifically inhibits guanine nucleoside biosynthesis in cultures of Erlich ascites tumour cells similar t o t h e inhibition by ribavirin. Ahluwalia et recently reported that