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Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses
Author(s) -
LINARDI R. L.,
STOKES A. M.,
BARKER S. A.,
SHORT C.,
HOSGOOD G.,
NATALINI C. C.
Publication year - 2009
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2009.01071.x
Subject(s) - methadone , pharmacokinetics , volume of distribution , pharmacology , analgesic , medicine , adverse effect , oral administration , opioid , anesthesia , chemistry , receptor
Methadone hydrochloride is a synthetic μ‐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.