Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses
Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses
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DOI：
10.2460/ajvr.73.2.290
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发表时间：
2012-02-01
影响因子：
1
通讯作者：
Short, Charles R.
中科院分区：
文献类型：
--
作者：
Linardi, Renata L.;Stokes, Ashley M.;Short, Charles R.
目的：研究马静脉、口服和灌胃给药后口服和注射用美沙酮制剂的生物利用度和药代动力学。动物-6匹健康成年马，单剂量(每匹马口服或灌胃给药0.15 mg/kg)或注射制剂(每匹马5个实验用药，每个实验用药间隔2周)。在每次给药前和给药后360分钟内从每匹马的预定时间点采集血样，用气相色谱-质谱仪测定血清药物浓度，并用非房室模型估计药代动力学参数。监测马匹的不良反应。结果：在接受治疗的马匹中，美沙酮的血清浓度等于或高于报告的人类有效浓度范围，没有诱导不良反应。马的口服药物动力学包括较短的半衰期(约1小时)、较高的生物利用度校正的全身清除量(5-8毫升/分钟/公斤)和较小的表观分布体积(校正的生物利用度为0.6-0.9 L/公斤)。口服美沙酮的生物利用度约为灌胃美沙酮的3倍。结论和临床相关性-由于美沙酮灌胃后的生物利用度低，美沙酮在马的小肠吸收似乎是有限的。更好地了解药物处置，包括吸收，可能会导致更合适的给药途径的选择，从而增强马的止痛作用，并将不良反应降至最低。(Am J Vet Res 2012；73：290-295)
Objective-To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses.Animals-6 healthy adult horses.Procedures-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.Results-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.Conclusions and Clinical Relevance-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. (Am J Vet Res 2012;73:290-295)