American journal of veterinary research2001; 62(5); 783-786; doi: 10.2460/ajvr.2001.62.783

Pharmacokinetics of imipramine in narcoleptic horses.

Abstract: To validate use of high-performance liquid chromatography (HPLC) in determining imipramine concentrations in equine serum and to determine pharmacokinetics of imipramine in narcoleptic horses. Methods: 5 horses with adult-onset narcolepsy. Methods: Blood samples were collected before (time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration of imipramine hydrochloride (2 or 4 mg/kg of body weight). Serum was analyzed, using HPLC, to determine imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed separately to estimate pharmacokinetic values. Results: Adverse effects (muscle fasciculations, tachycardia, hyperresponsiveness to sound, and hemolysis) were detected in most horses when serum imipramine concentrations were high, and these effects were most severe in horses receiving 4 mg of imipramine/kg. Residual adverse effects were not apparent. Value (mean +/- SD) for area under the curve was 3.9 +/- 0.7 h X microg/ml, whereas volume of distribution was 584 +/- 161.7 ml/kg, total body clearance was 522 +/- 102 ml/kg/h, and mean residence time was 1.8 +/- 0.6 hours. One horse had signs of narcolepsy 6 and 12 hours after imipramine administration; corrresponding serum imipramine concentrations were less than the therapeutic range. Conclusions: Potentially serious adverse effects may be seen in horses administered doses of imipramine that exceed a dosage of 2 mg/kg. Total body clearance of imipramine in horses is slower than that in humans; thus, the interval between subsequent doses should be longer in horses.
Publication Date: 2001-05-09 PubMed ID: 11341404DOI: 10.2460/ajvr.2001.62.783Google Scholar: Lookup
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Summary

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This research studied the effects and pharmacokinetics of a drug called imipramine in horses with narcolepsy, a sleep disorder. The researchers used a method called high-performance liquid chromatography (HPLC) to measure how the drug behaves within the body.

Research Methods

  • The study involved five adult horses suffering from narcolepsy.
  • These horses were administered imipramine hydrochloride intravenously at either 2 or 4 mg/kg of body weight.
  • Blood samples were collected at various intervals – before the administration and then at 3, 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 3, 4, 6, 8, 12, and 24 hours after the drug was given.
  • Utilizing HPLC, the serum was analyzed to determine the concentration of imipramine. The concentration-versus-time curve was assembled for each horse individually to ascertain pharmacokinetic values.

Findings

  • Adverse effects such as muscle contractions, rapid heart rate, increased sensitivity to sound, and hemolysis (breakdown of red blood cells) were observed in most horses when the serum imipramine concentration was high.
  • These adverse reactions were more severe in horses that were administered 4 mg of imipramine per kg of body weight. No value was found in residual adverse impacts.
  • The average values for various pharmacokinetic measures were reported: the area under the curve (3.9 h X microg/ml), volume of distribution (584 ml/kg), total body clearance (522 ml/kg/h), and mean residence time (1.8 hours).
  • One horse showed signs of narcolepsy 6 and 12 hours after administration of imipramine, where the serum imipramine concentrations were under the therapeutic range.

Conclusions

  • The study concluded that horses receiving doses of imipramine greater than 2 mg/kg could experience potentially serious side effects.
  • The total body clearance of imipramine in horses was slower than in humans, urging a conclusion that the interval between following doses of the drug should be longer in horses.

Cite This Article

APA
Peck KE, Hines MT, Mealey KL, Mealey RH. (2001). Pharmacokinetics of imipramine in narcoleptic horses. Am J Vet Res, 62(5), 783-786. https://doi.org/10.2460/ajvr.2001.62.783

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 62
Issue: 5
Pages: 783-786

Researcher Affiliations

Peck, K E
  • Texas A&M Veterinary Medical Diagnostic Laboratory, Texas A&M University, College Station 77843, USA.
Hines, M T
    Mealey, K L
      Mealey, R H

        MeSH Terms

        • Animals
        • Antidepressive Agents, Tricyclic / adverse effects
        • Antidepressive Agents, Tricyclic / blood
        • Antidepressive Agents, Tricyclic / pharmacokinetics
        • Area Under Curve
        • Chromatography, High Pressure Liquid / veterinary
        • Female
        • Horse Diseases / blood
        • Horse Diseases / drug therapy
        • Horse Diseases / metabolism
        • Horses / metabolism
        • Imipramine / adverse effects
        • Imipramine / blood
        • Imipramine / pharmacokinetics
        • Male
        • Narcolepsy / blood
        • Narcolepsy / drug therapy
        • Narcolepsy / metabolism
        • Narcolepsy / veterinary

        Citations

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