Knych Heather K, Steinmetz Stacy J, Traynham Megan L, McKemie Daniel S, Kass Philip H
K.L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Front Vet Sci. 2024 Sep 17;11:1461648. doi: 10.3389/fvets.2024.1461648. eCollection 2024.
Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed.
Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat.
The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration.
Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.
吗啡是一种对马有效的镇痛药，然而，治疗剂量的静脉注射已显示会产生剂量依赖性神经兴奋和不良的胃肠道效应。吗啡的镇痛作用至少部分归因于吗啡 - 6 - 葡萄糖醛酸（M6G）代谢物。给马口服会产生与静脉注射治疗剂量后相当的M6G浓度，且无不良反应。尚未报道其抗伤害感受作用。在本研究中，评估了单次和多次口服吗啡的热抗伤害感受作用。
六匹马接受单次静脉注射0.2mg/kg吗啡，并每12小时口服0.8mg/kg吗啡，持续4.5天。在给药过程中采集血样，测定吗啡和代谢物浓度并进行药代动力学分析。记录与药物相关的行为和生理反应。通过测定对热刺激的热阈值潜伏期来评估对有害刺激的反应。
与静脉注射相比，口服后M6G的最大浓度更高，且从2小时开始，吗啡和M6G的联合浓度超过静脉注射。单次和多次口服0.8mg/kg吗啡后，其提供并维持了与静脉注射吗啡相当的抗伤害感受作用，且不良反应更少。与静脉注射相比，口服吗啡耐受性良好，兴奋程度较低，对胃肠蠕动评分影响最小。
本研究结果值得进一步研究口服吗啡对马的抗伤害感受作用。
