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Lidocaine is an amide local anesthetic and clonidine is an antihypertensive (α2-adrenergic agonist). The use of these two drugs in combination is recommended to enhance the analgesic effect of lidocaine. The aim of this study was to investigate the influence of clonidine co-administration on the extent of lidocaine binding to rat serum, heart and maxillofacial tissues in vivo and in vitro. Thirty-two Wistar rats received either lidocaine alone, or lidocaine and clonidine, in the masseter muscle, and were then sacrificed 15 or 30 min after treatment. Serum, masseter, mandible and heart samples were then isolated and incubated in 0.9% NaCl solution for 12 h at 8°C. The extent of binding in the incubation medium and the serum was estimated by ultrafiltration, and the free lidocaine fraction was determined by the radioscopic method in a β-counter. An in vitro procedure was also performed. Serum, heart, masseter and mandible samples were incubated at 37°C for 15 or 30 min in Ringer's solution containing either lidocaine or lidocaine and clonidine, and the samples were similarly subjected to ultrafiltration. The percentage binding of lidocaine was again estimated by the radioscopic method. Lidocaine levels were found to be increased by clonidine co-administration in vivo and the free lidocaine fraction was enhanced in vitro as well in the examined tissues, obviously through mechanisms related to protein binding alterations.

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.