Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats

M. L. Mehl, Lisa A Tell, A. E. Kyles, Yi-Je Chen, A. Craigmill, C. R. Gregory

Research output: Contribution to journalArticle

Abstract

The pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide after intravenous (i.v.) and oral (p.o.) administration were evaluated in adult cats. Three treatments were administered: a single i.v. dose of A77 1726 (4mg/kg), a single oral dose of leflunomide (4mg/kg), and multiple oral doses of leflunomide (2mg/kg). Mean pharmacokinetic parameter values after a single i.v. dose of A77 1726 were distribution (A) and elimination (B) intercepts (15.2μg/mL and 34.5μg/mL, respectively), distribution and elimination half-lives (1.5 and 71.8h, respectively), area under the curve (AUC 0→∞; 3723μg*h/mL), mean residence time (MRT; 93h), clearance (Cl obs; 1.1mL/kg/h), and volume of distribution at steady state (Vd ss; 97mL/kg). Mean pharmacokinetic parameter values after a single oral dose of leflunomide were absorption and elimination rate constants (0.3 1/h and 0.01 1/h, respectively), absorption and elimination half-lives (2.3 and 59.1h, respectively), AUC 0→∞ (3966μg*h/mL), and maximum observed plasma concentration (C max; 38μg/mL). The bioavailability after a single oral dose of leflunomide was 100%. The mean±SD A77 1726 concentration that inhibited 50% lymphocytes (EC 50) was 16±13.5μg/mL. The mean±SD maximum A77 1726 concentration (EC max) was 61.0±23.9μg/mL.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume35
Issue number2
DOIs
StatePublished - Apr 2012

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

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