Plasma pharmacokinetics of warfarin enantiomers in cats

The purpose of this study was to determine the dispositions of S-warfarin a nd R-warfarin in normal cats following intravenous and oral administrations of racemic warfarin, Citrated blood samples were collected from 10 cats pr ior to and at times 5, 15, and 30 min, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 72 , 96, and 120 h following a single intravenous bolus of 0.5 mg/kg of racemi c warfarin. After a 21-day washout period, samples were then similarly coll ected in three groups of four cats for 120 h following oral administration of 0.1, 0.25, and 0.5 mg/kg racemic warfarin. S-warfarin and R-warfarin wer e detected using a high-performance liquid chromatography assay validated f or cat plasma. Drug concentration-time curves were subjected to non-compart mental analysis. Median pharmacokinetic parameters associated with the intr avenous administration of 0.5 mg/kg racemic warfarin were as follows: t(1/2 ) (S:28.2, R:18.3 h), area under the plasma concentration-time curve (AUC; S:33.0, R:24.6 h*mug/mL), area under the moment curve (AUMC; S:1889, R:527. 8 h*h*mug/mL), and mean residence time (MRT; S:38.7, R:20.9 h). For each pa rameter, S-warfarin was significantly different from R-warfarin (P < 0.05). Warfarin was absorbed rapidly after oral administration, and the dosage di d not affect the time to maximum concentration (S:0.87, R:0.75 h). Oral dos age significantly influenced maximum plasma concentration (ng/mL;, S:1267, R:1355 at 0.5 mg/kg; S:614.9, R:679.4 at 0.25 mg/kg; S:250.5, R:367.6 at 0. 1 mg/kg), AUC (h*<mu>g/mL, S:45.12, R:30.91 at 0.5 mg/kg; S:22.98:, R:18.99 at 0.25 mg/kg; S:3.922, R:3.570 at 0.1 mg/kg) and AUMC (h*h*mug/mL, S:2135 , R:1062 at 0.5 mg/kg; S:943.1, R:599.9 at 0.25 mg/kg; S:132.2, R:59.03 at 0.1 mg/kg), but not t(1/2) (S:23.5, R:11.6 h) nor MRT (S:26.3, R:13.5 h). B oth warfarin enantiomers were highly (> 96.5%) protein-bound. Quantitation of the warfarin content in commercially available tablets indicated an uneq ual distribution of the drug throughout the tablet.