Pharmacokinetics of amantadine in cats

This study reports the pharmacokinetics of amantadine in cats, after both i.v. and oral administration. Six healthy adult domestic shorthair female cats were used. Amantadine HCl (5 mg/kg, equivalent to 4 mg/kg amantadine base) was administered either intravenously or orally in a crossover randomized design. Blood samples were collected immediately prior to amantadine administration, and at various times up to 1440 min following intravenous, or up to 2880 min following oral administration. Plasma amantadine concentrations were determined by liquid chromatography-mass spectrometry, and plasma amantadine concentration-time data were fitted to compartmental models. A two-compartment model with elimination from the central compartment best described the disposition of amantadine administered intravenously in cats, and a one-compartment model best described the disposition of oral amantadine in cats. After i.v. administration, the apparent volume of distribution of the central compartment and apparent volume of distribution at steady-state [mean ± SEM (range)], and the clearance and terminal half-life [harmonic mean ± jackknife pseudo-SD (range)] were 1.5 ± 0.3 (0.7-2.5) L/kg, 4.3 ± 0.2 (3.7-5.0) L/kg, 8.2 ± 2.1 (5.9-11.4) mL·min/kg, and 348 ± 49 (307-465) min, respectively. Systemic availability [mean ± SEM (range)] and terminal half-life after oral administration [harmonic mean ± jackknife pseudo-SD (range)] were 130 ± 11 (86-160)% and 324 ± 41 (277-381) min, respectively.