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 language | English (US) |
|---|---|
| Pages (from-to) | 139-146 |
| Number of pages | 8 |
| Journal | Journal of Veterinary Pharmacology and Therapeutics |
| Volume | 35 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 2012 |
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ASJC Scopus subject areas
- Pharmacology
- veterinary(all)
Cite this
Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats. / Mehl, M. L.; Tell, Lisa A; Kyles, A. E.; Chen, Yi-Je; Craigmill, A.; Gregory, C. R.
In: Journal of Veterinary Pharmacology and Therapeutics, Vol. 35, No. 2, 04.2012, p. 139-146.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats
AU - Mehl, M. L.
AU - Tell, Lisa A
AU - Kyles, A. E.
AU - Chen, Yi-Je
AU - Craigmill, A.
AU - Gregory, C. R.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857996863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857996863&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2885.2011.01306.x
DO - 10.1111/j.1365-2885.2011.01306.x
M3 - Article
C2 - 21615755
AN - SCOPUS:84857996863
VL - 35
SP - 139
EP - 146
JO - Journal of Veterinary Pharmacology and Therapeutics
JF - Journal of Veterinary Pharmacology and Therapeutics
SN - 0140-7783
IS - 2
ER -