Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses.
Abstract: Methadone hydrochloride is a synthetic mu-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (V(d)/F) and short elimination half-life (t(1/2)). The mean of the estimated t(1/2) (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated C(max) (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively.
Publication Date: 2009-09-17 PubMed ID: 19754917DOI: 10.1111/j.1365-2885.2009.01071.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the effects and pharmacokinetics (the body’s processing of a drug) of orally-administered methadone hydrochloride in horses, concluding that the arrangement of methadone followed first order elimination and had rapid absorption and elimination phases.
Research Goals
- The primary goal was to understand the pharmacokinetics of oral methadone in horses, a study which has not been undertaken before.
- The researchers aimed to administer various doses of the opioid and record its physical effects in healthy horses.
Methodology
- 12 adult horses were given oral doses of methadone (0.1, 0.2, and 0.4 mg/kg).
- Serum methadone concentrations were then measured over 24 hours using gas chromatography/mass spectrometry, a method effectively used in drug detection and quantification studies.
- The pharmacokinetic parameters were estimated using a non-compartmental model, a simple and flexible approach that was selected for its ability to analyze drug concentration over time.
- All physical effects were observed and recorded by experienced clinicians to ensure reliable data collection.
Results and Observations
- The study found no adverse effects or toxicity in the horses after the ingestion of methadone, making it a potentially viable medical treatment for the equine species.
- Methadone demonstrated first-order elimination, meaning that it was rapidly absorbed and expelled from the horse’s system, and its elimination was dependent on the concentration of the drug.
- The pharmacokinetic profile was characterized by high clearance (Cl/F), a small volume of distribution (V(d)/F), and short elimination half-life (t(1/2)), indicating that the drug is quickly eliminated from the horse’s body.
- The estimated elimination half-life and the maximum concentration (C(max)) of methadone at each given dose were recorded, providing important data for future studies on drug dosage and administration timing.
Cite This Article
APA
Linardi RL, Stokes AM, Barker SA, Short C, Hosgood G, Natalini CC.
(2009).
Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses.
J Vet Pharmacol Ther, 32(5), 492-497.
https://doi.org/10.1111/j.1365-2885.2009.01071.x Publication
Researcher Affiliations
- Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA. rlinardi@vetmed.lsu.edu
MeSH Terms
- Administration, Oral
- Analgesics, Opioid / administration & dosage
- Analgesics, Opioid / blood
- Analgesics, Opioid / pharmacokinetics
- Animals
- Dose-Response Relationship, Drug
- Female
- Horses
- Male
- Methadone / administration & dosage
- Methadone / blood
- Methadone / pharmacokinetics
Citations
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