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  • Title: Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses.
    Author: Linardi RL, Stokes AM, Barker SA, Short C, Hosgood G, Natalini CC.
    Journal: J Vet Pharmacol Ther; 2009 Oct; 32(5):492-7. PubMed ID: 19754917.
    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.
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