Pharmacokinetics of etodolac in the horse following oral and intravenous administration.
Abstract: The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally, in vitro cyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two-way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3-week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half-life (t(1/2)) of 2.67 h, volume of distribution (Vd) of 0.29 L/kg and clearance (Cl) of 234.87 mL/h kg. Following oral administration, the average maximum plasma concentration (Cmax)) was 32.57 mug/mL with a t(1/2) of 3.02 h. Bioavailability was approximately 77.02%. Results of in vitro COX selectivity assays showed that etodolac was only slightly selective for COX-2 with a COX-1/COX-2 selectivity ratio effective concentration (EC)50 of 4.32 and for EC80 of 4.77. This study showed that etodolac is well absorbed in the horse after oral administration, and may offer a useful alternative for anti-inflammatory treatment of various conditions in the horse.
Publication Date: 2007-01-16 PubMed ID: 17217400DOI: 10.1111/j.1365-2885.2007.00811.xGoogle Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Anti-inflammatory
- Bioavailability
- Biological Half-Life
- Clinical Study
- Cyclooxygenase
- Disease Treatment
- Drug
- Equine Diseases
- Equine Health
- High-performance Liquid Chromatography (HPLC)
- Horses
- In Vitro Research
- In Vivo
- Intravenous Administration
- NSAID
- Oral Administration
- Pharmacokinetics
- Physiology
- Plasma
- Veterinary Medicine
Summary
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The research study investigated how the drug etodolac is absorbed and distributed in horses when administered orally and intravenously. The study also included in-vitro analysis of the drug’s selectivity for two types of enzymes.
Understanding the Research
- The study focused on understanding the pharmacokinetics of etodolac in horses. Pharmacokinetics is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. It mainly focuses on the rates of absorption, distribution, metabolism, and excretion of drugs.
- Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) used for severe pain, inflammation, or fever. Six horses were randomly chosen to take etodolac via oral or intravenous methods in a two-way crossover design. This means that all horses experienced both routes of administration, with a minimum 3-week break in between—known as a washout period—to prevent any interaction between the results.
- The drug dosage administered was 20mg/kg, and plasma samples were taken after administration for analysis. The method used to determine the concentration of etodolac in the horse plasma was high pressure liquid chromatography with ultraviolet detection – a common method used for detecting specific substances in a liquid mixture.
Finding and Implications
- The study showed that after intravenous administration of etodolac, the mean plasma half-life was 2.67 hours. The half-life of a drug is the time taken by the body to reduce the concentration of the drug by half. The volume of distribution was 0.29 L/kg, which is the theorized volume that would be necessary to contain the total drug administered at the same concentration that it is observed in the blood plasma.
- The clearance was 234.87 mL/h kg, indicating the volume of plasma from which a substance is completely removed per unit time.
- When administered orally, the average maximum plasma concentration was 32.57 µg/mL, with a half-life of 3.02 hours. The bioavailability, which is the portion of the original drug dose that reaches the systemic circulation, was approximately 77.02%. These findings suggest that etodolac is well absorbed in horses when administered orally.
- Finally, in vitro analysis, which is done outside the living organism, was carried out to determine the selectivity of etodolac for COX-1/COX-2. COX-1 and COX-2 are two variants of the enzyme cyclooxygenase, which is involved in the inflammation process. The results showed that etodolac was not significantly selective for one type of COX over the other.
- Based on these observations, the researchers concluded that etodolac could be a useful alternative anti-inflammatory treatment in horses. This is important as safe and effective pain management is a critical aspect of veterinary medicine.
Cite This Article
APA
Davis JL, Papich MG, Morton AJ, Gayle J, Blikslager AT, Campbell NB.
(2007).
Pharmacokinetics of etodolac in the horse following oral and intravenous administration.
J Vet Pharmacol Ther, 30(1), 43-48.
https://doi.org/10.1111/j.1365-2885.2007.00811.x Publication
Researcher Affiliations
- Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27606, USA.
MeSH Terms
- Administration, Oral
- Animals
- Area Under Curve
- Cross-Over Studies
- Cyclooxygenase 1 / drug effects
- Cyclooxygenase 2 / drug effects
- Cyclooxygenase Inhibitors / administration & dosage
- Cyclooxygenase Inhibitors / blood
- Cyclooxygenase Inhibitors / pharmacokinetics
- Cyclooxygenase Inhibitors / pharmacology
- Etodolac / administration & dosage
- Etodolac / blood
- Etodolac / pharmacokinetics
- Etodolac / pharmacology
- Female
- Horses / metabolism
- Injections, Intravenous / veterinary
- Male
Citations
This article has been cited 4 times.- Mercer MA, Davis JL, McKenzie HC. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses.. Animals (Basel) 2023 May 10;13(10).
- Jacobs CC, Schnabel LV, McIlwraith CW, Blikslager AT. Non-steroidal anti-inflammatory drugs in equine orthopaedics.. Equine Vet J 2022 Jan 25;54(4):636-48.
- Ziegler A, Fogle C, Blikslager A. Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs in horses.. J Am Vet Med Assoc 2017 Jun 1;250(11):1271-1274.
- Marañón G, Manley W, Cayado P, García C, de la Muela MS, Vara E. Alterations in the glutathione metabolism could be implicated in the ischemia-induced small intestinal cell damage in horses.. BMC Vet Res 2009 Mar 18;5:10.
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