Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza virus A2

Abstract

Objective - To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses. Animals - 5 clinically normal horses and 8 horses seronegative to influenza A. Procedure - Horses were given rimantadine (7 mg/kg of body weight, IV, once; 15 mg/kg, PO, once; 30 mg/kg, PO once; and 30 mg/kg, PO, q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, PO, q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. Results - Estimated mean peak plasma concentration of rimantadine after IV administration was 2.0 μg/ml, volume was distribution (mean ± SD) at steady-state (Vd(ss)) was 7.1 ± 1.7 L/kg, plasma clearance after IV administration was 51 ± 7 ml/min/kg, and β-phase half-life was 2.0 ± 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 05 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean biovailability (F) of 25%, β-phase half-life of 2.2 ± 0.3 hours, and clearance of 340 ± 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and through concentrations (mean ± SEM) of 811 ± 97 and 161 ± 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds. Conclusions and Clinical Relevance - Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.