Tigka E, Kotsiou A, Saranteas T, Mourouzis J, Kostopanagiotou G, Tesseromatis C
Department of Pharmacology, Medical School, University of Athens, Athens, Hellas.
Eur J Drug Metab Pharmacokinet. 2009 Jul-Sep;34(3-4):229-32. doi: 10.1007/BF03191178.
Lidocaine is a local anaesthetic widely used in regional and epidural anaesthesia. Clonidine a alpha2-adrenergic agonist is an antihypertensive agent, regulating the production of catecholamines (epinephrine and norepinephrine) and added to local anesthetic infusions in order to improve postoperative analgesia. The aim of the study was to investigate the influence of clonidine co-administration on the binding of 14C lidocaine to rat serum and heart tissue protein as well as its pharmacodynamic effects in the heart. Four groups of Wistar rats (n=7) were used; Groups I and II received 4 mg/kg lidocaine i.m. Groups III and IV received lidocaine and 1 microg/kg clonidine i.m. In group I and III fifteen minutes and in groups II and IV thirty minutes after the initial treatment, ultrasound examination of heart function (heart rate, diameter of left ventricle in systole and diastole, ejection fraction) was performed. The animals were then sacrificed in all groups. Lidocaine free fraction in serum and heart was evaluated via ultrafiltration. The kinetics of lidocaine was altered by clonidine co-administration probably by mechanisms related to protein binding alterations. However, the pharmacokinetic interactions were not accompanied by changes of pharmacodynamic parameters including those of heart function as measured by echocardiography.
利多卡因是一种广泛用于区域麻醉和硬膜外麻醉的局部麻醉剂。可乐定是一种α2肾上腺素能激动剂，是一种抗高血压药物，可调节儿茶酚胺（肾上腺素和去甲肾上腺素）的产生，并添加到局部麻醉剂输注中以改善术后镇痛效果。本研究的目的是调查可乐定联合用药对14C利多卡因与大鼠血清和心脏组织蛋白结合的影响及其在心脏中的药效学作用。使用了四组Wistar大鼠（n = 7）；第一组和第二组肌肉注射4 mg/kg利多卡因。第三组和第四组肌肉注射利多卡因和1 μg/kg可乐定。在第一组和第三组初始治疗后15分钟以及第二组和第四组初始治疗后30分钟，进行心脏功能超声检查（心率、左心室收缩期和舒张期直径、射血分数）。然后对所有组的动物实施安乐死。通过超滤评估血清和心脏中利多卡因的游离分数。可乐定联合用药可能通过与蛋白质结合改变相关的机制改变了利多卡因的动力学。然而，药代动力学相互作用并未伴随着药效学参数的变化，包括通过超声心动图测量的心脏功能参数。
