SATURABLE IN-VITRO METABOLISM OF ARTICAINE BY SERUM ESTERASES - DOES IT CONTRIBUTE TO THE PERSISTENCE OF THE LOCAL-ANESTHETIC EFFECT

Background and Objectives. The amide-type local anesthetic articaine i s unique in that hydrolysis to articainic acid by serum esterases is i ts main metabolic pathway. The purpose of the present investigation wa s to study the concentration dependence of this pathway in vitro. Meth ods. To unbuffered (pH 8.2) as well as phosphate-buffered (pH 7.4) hea ted serum samples were added various amounts of articaine in the range 10-300 mu g/mL. Concentrations of articaine and articainic acid were measured by high-performance liquid chromatography after incubating th e samples at 37 degrees C for intervals ranging from 5 minutes to 6 ho urs after addition of articaine. Results. The in vitro metabolism of a rticaine was shown to undergo pH-dependent Michaelis-Menten kinetics, indicating saturation at higher substrate concentrations. The Michaeli s constant K-m was determined as 175 mu g/mL and 22.1 mu ug/mL and the maximum reaction rate V-max as 2.1 mu g/mL/min and 0.17 mu g/mL/min a t pH 8.2 and pH 7.2, respectively. These results support previous in v iva observations that suggest saturable articaine metabolism, indicate d by higher articaine/articainic acid metabolic ratio with higher arti caine concentrations in alveolar blood after dental extraction. Conclu sion. Local saturation of the serum esterases may contribute to the ad vantageous relationship between persistence of the local anesthetic ef fect and low systemic toxicity caused by the fast systemic elimination of articaine tie, its wide toxic therapeutic ratio).