Pharmacokinetics of mequindox and one of its major metabolites in chickens after intravenous, intramuscular and oral administration

Abstract

Pharmacokinetics of mequindox and one of its major metabolites (M) was determined in chickens after intravenous (i.v.), intramuscular (i.m.) and oral administration of mequindox at a single dose of 10 (i.v. and i.m.) or 20mg/kg b.w. (oral). Plasma concentration profiles were analyzed by a non-compartmental pharmacokinetic method. Following i.v., i.m. and oral administration, the areas under the plasma concentration–time curve (AUC0–∞) were 0.71±0.15, 0.67±0.21, 0.25±0.10μgh/mL (mequindox) and 37.24±7.98, 36.40±9.16, 86.39±16.01μgh/mL (M), respectively. The terminal elimination half-lives (t1/2λz) were determined to be 0.15±0.06, 0.21±0.09, 0.49±0.23h (mequindox) and 5.36±0.86, 5.39±0.52, 5.22±0.35h (M), respectively. The bioavailabilities (F) of mequindox were 89.4% and 16.6% for i.m. and oral administration. Steady-state distribution volume (Vss) of 1.20±0.34L/kg and total body clearance (ClB) of 13.57±2.16L/kgh were determined for mequindox after i.v. dosing. After single i.m. and oral administration, peak plasma concentrations (Cmax) of 3.04±1.32, 0.36±0.13μg/mL (mequindox) and 3.81±0.92, 5.99±1.16μg/mL (M) were observed at tmax of 0.08±0.02, 0.32±0.12h (mequindox) and 0.66±0.19, 6.67±1.03h (M), respectively. The results showed that mequindox was rapidly absorbed after i.m. or p.o. administration and most of mequindox was transformed to metabolites in chickens, with much higher Cmaxs and AUCs of metabolite (M) than those of mequindox in plasma.