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Am J Vet Res. 1999 Jul;60(7):888-94.

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

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  • 1Graduate Center for Toxicology, Maxwell H. Gluck Equine Research Center, Lexington, KY, USA.

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, 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.

PMID:
10407485
[PubMed - indexed for MEDLINE]
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