KuKanich B, KuKanich K, Black J
Department of Anatomy and Physiology, Institute of Computational Comparative Medicine, Manhattan, KS, USA.
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
J Vet Pharmacol Ther. 2017 Dec;40(6):e54-e61. doi: 10.1111/jvp.12424. Epub 2017 Jun 11.
Tramadol is administered to dogs for analgesia but has variability in its extent of absorption, which may hinder its efficacy. Additionally, the active opioid metabolite (M1) occurs in low concentrations. The purpose of this study was to determine if administration of oral tramadol with suspected metabolism inhibitors (ketoconazole, cimetidine) would lead to improved bioavailability of tramadol and M1. Six healthy Greyhounds were included. They were administered tramadol orally and intravenously, M1 intravenously, oral tramadol with oral ketoconazole and oral tramadol with oral cimetidine. Oral tramadol bioavailability was low (2.6%). Ketoconazole and cimetidine significantly increased tramadol bioavailability to 18.2% and 20.3%, respectively. The mean maximum plasma concentration of tramadol alone was 22.9 ng/ml, and increased to 109.9 and 143.2 μg/ml with ketoconazole and cimetidine, respectively. However, measured tramadol plasma concentrations were below the minimum concentration considered effective in humans (228 μg/ml). In all treatment groups, measured M1 concentrations (<7 μg/ml) were below concentrations associated with efficacy in humans. To conclude, tramadol and M1 concentrations were low and variable in dogs after oral dosing of tramadol, even in combination with cimetidine or ketoconazole, but effective concentrations in dogs have not been defined.
曲马多用于犬类镇痛，但吸收程度存在差异，这可能会影响其疗效。此外，活性阿片类代谢物（M1）的浓度较低。本研究的目的是确定口服曲马多与疑似代谢抑制剂（酮康唑、西咪替丁）联合使用是否会提高曲马多和M1的生物利用度。纳入了6只健康的灵缇犬。分别对它们口服和静脉注射曲马多、静脉注射M1、口服曲马多与口服酮康唑联合以及口服曲马多与口服西咪替丁联合。口服曲马多的生物利用度较低（2.6%）。酮康唑和西咪替丁分别将曲马多的生物利用度显著提高至18.2%和20.3%。单独使用曲马多时，血浆平均最大浓度为22.9 ng/ml，与酮康唑和西咪替丁联合使用时分别增至109.9和143.2 μg/ml。然而，测得的曲马多血浆浓度低于人类有效浓度（228 μg/ml）。在所有治疗组中，测得的M1浓度（<7 μg/ml）低于与人类疗效相关的浓度。总之，口服曲马多后，犬类体内曲马多和M1的浓度较低且存在差异，即使与西咪替丁或酮康唑联合使用也是如此，但犬类的有效浓度尚未确定。
