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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.

The influence of clonidine co-administration on the extent of lidocaine protein binding to rat serum and tissues