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

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, i.v., once; 15 mg/kg, p.o., once; 30 mg/kg, p.o., once; and 30 mg/kg, p.o., 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, p.o., q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus. RESULTS: Estimated mean peak plasma concentration of rimantadine after i.v. administration was 2.0 micrograms/ml, volume of distribution (mean +/- SD) at steady-state (Vdss) was 7.1 +/- 1.7 L/kg, plasma clearance after i.v. administration 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 concentrations 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 bioavailability (F) of 25%, beta-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 trough 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.

Lack of local anaesthetic efficacy of Sarapin in the abaxial sesamoid block model.

Sarapin is a distillate of the pitcher plant that has long been used in human and veterinary medicine for 'regional analgesia'. The mechanism of the reported analgesic response is unknown; however, the agent is purported to provide more effective analgesia for slow, chronic pain than for sharp, acute pain. Reportedly, Sarapin is also widely used as an analgesic agent in the horse, generally in combination with corticosteroids and other agents. To determine its local anaesthetic efficacy in the horse, we tested Sarapin in a unilateral abaxial sesamoid block model at two dose levels, 2 mL and 10 mL per site, respectively. Cutaneous pain was induced with a light/heat lamp, and analgesia was assessed by measuring the hoof-withdrawal reflex latency period. Neither dose of Sarapin altered hoof-withdrawal reflex latency in this experimental model tested over a two-week period. Based on the demonstrated efficacy of this local anaesthetic model, it seems clear that Sarapin has no significant classical local anaesthetic actions in the horse, and probably not in other species either.