Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A
Koret School of Veterinary Medicine, Faculty of Agricultural, Food and Environmental Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
J Vet Pharmacol Ther. 2008 Feb;31(1):60-5. doi: 10.1111/j.1365-2885.2007.00929.x.
Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations. Tramadol clearance, apparent volume of distribution at steady-state, mean residence time (MRT) and half-life after intravenous administration were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively. The MRT and half-life after intramuscular administration were 155+/-23 and 92+/-14 min. The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%. Tramadol was poorly absorbed after oral administration and only 3% of the administered dose was found in systemic circulation. The fate of the tramadol M1 metabolite was also investigated. M1 appeared to be a minor metabolite in horses, which could hardly be detected in plasma samples. The poor bioavailability after oral administration and the short half-life of tramadol may restrict its usefulness in clinical applications.
曲马多是一种中枢性镇痛药，在过去二十年中已在临床上用于治疗人类的中度至中度重度疼痛。本研究通过静脉内、肌肉内、口服速释剂型和口服缓释剂型途径研究了曲马多在马匹中的给药情况。七匹马用于四交叉研究设计，其中外消旋曲马多通过每种给药途径以2mg/kg的剂量给药。总共在0至2880分钟之间采集了23份血样。通过使用LC/MS/MS方法测定所获得的血浆样品中曲马多及其M1代谢物的浓度，并用于药代动力学计算。静脉内给药后曲马多的清除率、稳态分布表观容积、平均驻留时间（MRT）和半衰期分别为26±3mL/min/kg、2.17±0.52L/kg、83±10分钟和82±10分钟。肌肉内给药后的MRT和半衰期分别为155±23和92±14分钟。平均吸收时间为72±22分钟，生物利用度为111±39%。口服给药后曲马多吸收较差，在体循环中仅发现3%的给药剂量。还研究了曲马多M1代谢物的转归。M1似乎是马匹中的一种次要代谢物，在血浆样品中几乎检测不到。口服给药后生物利用度差以及曲马多半衰期短可能会限制其在临床应用中的效用。
