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

Abstract: 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.
Publication Date: 1999-07-17 PubMed ID: 10407485
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  • Clinical Trial
  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

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This research article explores the effects of rimantadine, a pharmaceutical drug, on horses that have been deliberately infected with the influenza virus A2. The objective was to understand the kinetics of rimantadine in the system of the horse, and further establish its efficiency when used preemptively, to combat the virus symptoms.

Methods & Process

  • The experiment was conducted on 13 horses, five of which were clinically normal, and eight were seronegative to the influenza virus A2.
  • The horses were administered with varying doses of rimantadine hydrochloride to ascertain the distribution kinetics of the drug. The assumption was that the results would detail the path of the drug in the horse’s body and its interaction with the system over the time.
  • In order to assess the effectiveness of rimantadine on induced infections, horses that were seronegative to the influenza virus were purposely infected (challenge-exposed) and observed. The particular strain of the virus used was A2, and the procedure was commenced 12 hours after the administration of the drug.

Findings

  • The primary findings from the research showed that the peak plasma concentration in the horses’ systems was around 2.0 micrograms/ml after intravenous administration of the drug.
  • Further observations in the kinetic parameters indicated that the volume of distribution (Vdss) was 7.1 +/- 1.7 L/kg, and the plasma clearance rate post administration was 51 +/- 7 ml/min/kg. The beta-phase half-life was 2.0 +/- 0.4 hours.
  • The peak plasma concentrations after oral administration of 15 mg of rimantadine per kg of weight were less than 50 ng/ml after three hours of administration.
  • However, a single oral administration of 30 mg/kg yielded a significantly higher plasma concentration of 500 ng/ml, with a bioavailability of 25%, beta-phase half-life of 2.2 +/- 0.3 hours, and a clearance rate of 340 +/- 255 ml/min/kg.
  • Observations were also noted for horses after multiple doses of rimantadine, and the steady-state concentrations were recorded.
  • Preemptive use of rimantadine in horses deliberately infected with the A2 virus led to significant decreases in rectal temperature and lung sounds, indicating improvement in the health condition of the horses.

Conclusion

  • The research has come to the conclusion that rimantadine, when orally administered to horses, can effectively reduce the clinical signs of influenza virus infection.

Cite This Article

APA
Rees WA, Harkins JD, Lu M, Holland RE, Lehner AF, Tobin T, Chambers TM. (1999). Pharmacokinetics and therapeutic efficacy of rimantadine in horses experimentally infected with influenza virus A2. Am J Vet Res, 60(7), 888-894.

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 60
Issue: 7
Pages: 888-894

Researcher Affiliations

Rees, W A
  • Graduate Center for Toxicology, Maxwell H. Gluck Equine Research Center, Lexington, KY, USA.
Harkins, J D
    Lu, M
      Holland, R E
        Lehner, A F
          Tobin, T
            Chambers, T M

              MeSH Terms

              • Administration, Oral
              • Animals
              • Antibodies, Viral / blood
              • Antiviral Agents / administration & dosage
              • Antiviral Agents / blood
              • Antiviral Agents / pharmacokinetics
              • Antiviral Agents / standards
              • Area Under Curve
              • Biological Availability
              • Chick Embryo
              • Female
              • Gas Chromatography-Mass Spectrometry / veterinary
              • Hemagglutination Inhibition Tests / veterinary
              • Horse Diseases / drug therapy
              • Horse Diseases / virology
              • Horses
              • Injections, Intravenous / veterinary
              • Microbial Sensitivity Tests
              • Nasal Mucosa / virology
              • Orthomyxoviridae / drug effects
              • Orthomyxoviridae Infections / drug therapy
              • Orthomyxoviridae Infections / veterinary
              • Rimantadine / administration & dosage
              • Rimantadine / blood
              • Rimantadine / pharmacokinetics
              • Rimantadine / standards

              Citations

              This article has been cited 2 times.
              1. Chambers TM, Balasuriya UB, Reedy SE, Tiwari A. Replication of avian influenza viruses in equine tracheal epithelium but not in horses. Influenza Other Respir Viruses 2013 Dec;7 Suppl 4(Suppl 4):90-3.
                doi: 10.1111/irv.12188pubmed: 24224824google scholar: lookup
              2. Kelly JM, Quack G, Miles MM. In vitro and in vivo activities of aminoadamantane and aminoalkylcyclohexane derivatives against Trypanosoma brucei. Antimicrob Agents Chemother 2001 May;45(5):1360-6.