Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug.
Abstract: Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive days. Seventeen venous blood samples were collected from each horse after the single dose study and again after the last dose on day 42. Plasma phenobarbital concentration was determined by use of a fluorescence assay validated for horses. Additional blood samples (n = 11) were collected on days 8 and 25 to determine peak and trough concentrations, as well as total body clearance. Phenobarbital disposition followed a one-compartment model. Mean kinetic variables after single and repeated orally administered doses (42 days) were: elimination half-life = 24.2 +/- 4.7 and 11.2 +/- 2.3 hours, volume of distribution = 0.960 +/- 0.060 and 0.914 +/- 0.119 L/kg, and clearance = 28.2 +/- 5.1 and 57.3 +/- 9.6 ml/h/kg, respectively. Results indicated that significant (P less than 0.05) difference in half-life and oral clearance existed between single and repeated dosing. The significant decrease in half-life after repeated dosing with phenobarbital may be indicative of enzyme induction. Significant difference was not observed between baseline serum enzyme concentration and concentration measured on day 42, except for gamma-glutamyltransferase activity, which was significantly increased on day 42 in 3 of the 6 horses. On the basis of increases in oral clearance observed over 42 days, dose adjustments may be required.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1992-05-01 PubMed ID: 1524295
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The study examines how phenobarbital, a medicine usually used to treat seizures, is processed in the bodies of horses. It was found that the time it took for the drug to be eliminated from the body and how fast it was cleared from the body, changed significantly when the horses were given repeated doses of the drug over 42 days.
Study Design and Procedures
- The research involved six healthy fully grown horses who received a single dose of phenobarbital at 26 mg/kg of body weight, followed by multiple 13 mg/kg doses for 42 consecutive days.
- Seventeen venous blood samples were taken from each horse after the single dose, and then again after the final dose on day 42. The samples were analyzed to determine the plasma concentration of phenobarbital in the horses’ bloodstream.
- The researchers used a fluorescence assay, a tool that can measure the presence of specific substances in a sample, validated for use in horses to determine the concentration of phenobarbital.
- Additional blood samples were taken on days 8 and 25 to establish peak and trough concentrations as well as the overall body clearance of the drug.
Results and Interpretation
- After analysis, it was found that the average values for time taken for elimination of the drug from the body, volume of distribution in the body and clearance from the body varied after a single dose versus repeated doses over 42 days.
- The half-life of the drug (time taken for the drug quantity to reduce to half) decreased from around 24.2 hours after a single dose to around 11.2 hours after repeated doses.
- Additionally, the oral clearance rate (how fast the body eliminates the drug) increased significantly with repeated dosing.
- These changes suggest an induced enzyme response, where the body adapts to the repeated presence of the drug and processes it faster over time. This is highlighted by the significant increase of the enzyme gamma-glutamyltransferase activity in three out of the six horses after 42 days of dosing.
- The researchers concluded that because oral clearance increased over the 42 days, dosage adjustments may be needed when giving phenobarbital to horses over longer periods of time.
Cite This Article
APA
Knox DA, Ravis WR, Pedersoli WM, Spano JS, Nostrandt AC, Krista LM, Schumacher J.
(1992).
Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug.
Am J Vet Res, 53(5), 706-710.
Publication
Researcher Affiliations
- Department of Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, AL 36849.
MeSH Terms
- Absorption
- Administration, Oral
- Animals
- Half-Life
- Horses / metabolism
- Liver / drug effects
- Phenobarbital / administration & dosage
- Phenobarbital / adverse effects
- Phenobarbital / pharmacokinetics
- Tissue Distribution
Grant Funding
- FDA-U-000059-02 / FDA HHS
Citations
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