Linardi Renata L, Stokes Ashley M, Keowen Michael L, Barker Steven A, Hosgood Giselle L, Short Charles R
Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, 70803, USA.
Am J Vet Res. 2012 Feb;73(2):290-5. doi: 10.2460/ajvr.73.2.290.
To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses.
6 healthy adult horses.
Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects.
In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration.
Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.
在马经静脉注射、口服和胃内给药后，对美沙酮口服和注射制剂的生物利用度及药代动力学特征进行描述。
6匹健康成年马。
马分别经口服、胃内给药或静脉注射接受单剂量（每剂0.15mg/kg）的盐酸美沙酮口服制剂或该药物的注射制剂（每匹马5种实验处理；每种实验处理之间有2周的洗脱期）。在每次给药后的360分钟内，于预定时间点之前和各时间点采集每匹马的血样，通过气相色谱 - 质谱分析测定血清药物浓度，并使用非房室模型估算药代动力学参数。对马进行不良反应监测。
在接受治疗的马中，血清美沙酮浓度等于或高于报道的人类有效浓度范围，且未诱发不良反应。马的口服药代动力学特征包括半衰期短（约1小时）、经生物利用度校正后的全身清除率高（5至8mL/分钟/千克）以及经生物利用度校正后的表观分布容积小（0.6至0.9L/千克）。口服美沙酮的生物利用度约为胃内给药的3倍。
由于胃内给药后生物利用度低，马小肠中美沙酮的吸收似乎受限。更好地了解药物处置情况，包括吸收情况，可能会导致更合适的给药途径选择，从而增强镇痛效果并使马的不良反应最小化。
