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.


METHODS
5 clinically normal horses and 8 horses seronegative to influenza A.


METHODS
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
Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection.
Rees
W A
WA
Graduate Center for Toxicology, Maxwell H. Gluck Equine Research Center, Lexington, KY, USA.
Harkins
J D
JD
Lu
M
M
Holland
R E
RE
Lehner
A F
AF
Tobin
T
T
Chambers
T M
TM
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000592:standards; D019540:Area Under Curve; D001682:Biological Availability; D002642:Chick Embryo; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000662:veterinary; D006385:Hemagglutination Inhibition Tests / Q000662:veterinary; D006734:Horse Diseases / Q000188:drug therapy* / Q000821:virology; D006736:Horses; D007275:Injections, Intravenous / Q000662:veterinary; D008826:Microbial Sensitivity Tests; D009297:Nasal Mucosa / Q000821:virology; D009975:Orthomyxoviridae / Q000187:drug effects*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000662:veterinary*; D012299:Rimantadine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000592:standards
D000914:Antibodies, Viral; D000998:Antiviral Agents; D012299:Rimantadine