Vainionpää Mari H, Raekallio Marja R, Pakkanen Soile A E, Ranta-Panula Ville, Rinne Valtteri M, Scheinin Mika, Vainio Outi M
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Vet Anaesth Analg. 2013 May;40(3):257-64. doi: 10.1111/vaa.12012. Epub 2013 Jan 31.
To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine.
Experimental randomized blinded crossover study.
Six healthy horses.
Detomidine (10 μg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 μg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed ) and pharmacokinetic parameters. Significance was set at p < 0.05.
A significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance.
MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses.
研究血浆药物浓度以及MK - 467（L - 659'066）对静脉注射（IV）地托咪定镇静的马匹的镇静效果、心率和肠道蠕动的影响。
实验性随机双盲交叉研究。
六匹健康马匹。
单独给予地托咪定（10μg kg⁻¹静脉注射）（DET）以及与MK - 467联合使用（250μg kg⁻¹静脉注射；DET + MK）。对镇静水平和肠鸣音进行评分。测量心率（HR）和中心静脉压（CVP）。采集血液以测定血浆药物浓度。对HR、CVP和肠鸣音采用重复测量方差分析，对镇静时间曲线下面积（AUCsed）和药代动力学参数的处理间两两比较采用学生t检验。显著性设定为p < 0.05。
DET给药后HR显著降低，且DET + MK组的HR显著高于单独使用DET组。在任何接受DET + MK治疗的马匹中均未检测到心脏传导阻滞。DET + MK减轻了DET给药后早期检测到的CVP升高，但随后两种治疗方式下CVP均下降。MK - 467预防了地托咪定诱导的肠道运动减弱。DET组的AUCsed显著高于DET + MK组，但两种治疗方式下的最大镇静评分无显著差异。MK - 467降低了地托咪定血浆浓度的AUC，并增加了其分布容积和清除率。
MK - 467预防了地托咪定诱导的心动过缓和肠道运动减弱。MK - 467不影响地托咪定诱导镇静的临床质量，但作用持续时间缩短，这可能是由于MK - 467对地托咪定血浆浓度的影响所致。MK - 467在临床上可能有助于预防马匹中地托咪定的某些外周副作用。
