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

Objective-To determine pharmacokinetics of single and multiple doses of rim antadine hydrochloride in horses and to evaluate prophylactic efficacy of r imantadine 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 det ermined in horses seronegative to influenza virus A2. Rimantadine was admin istered (30 mg/kg, PO, q 12 h for 7 days) beginning 12 hours before challen ge-exposure to the virus. Results-Estimated mean peak plasma concentration of rimantadine after IV ad ministration was 2.0 mu g/ml, volume of distribution (mean +/- SD) at stead y-state (Vd(ss)) was 7.1 +/- 1.7 L/kg, plasma clearance after IV administra tion was 51 +/- 7 ml/min/kg, and beta-phase half life was 2.0 +/- 0.4 hours . Oral administration of 15 mg of rimantadine/kg yielded peak plasma concen trations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg /kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavail ability (F) of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and clearanc e of 340 +/- 255 ml/min/kg. Multiple doses of rimantadine provided steady-s tate concentrations in plasma with peak and trough concentrations (mean +/- SEM) of 811 +/- 97 and 161 +/- 12 ng/ml, respectively. Rimantadine used pr ophylactically 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 ho rses can safely ameliorate clinical signs of influenza virus infection.