Study on Brain Uptake of Local Anesthetics in Rats

Abstract

Brain uptake of local anesthetics under steady-state plasma condition and/or following intravenous bolus administration was investigated in rats. All ester-type anesthetics examined such as ethyl (Et), propyl (Pr), butyl (Bu) esters of p-aminobenzoic acid (PABA), and procaine disappeared rapidly from plasma in a dose-dependent manner. Plasma profiles of these compounds were well explained by a 2-compartment model with a Michaelis-Menten type elimination process from a central compartment. On the other hand, lidocaine, amide-type anesthetic, showed a linear pharmacokinetic characteristic and its half life in the elimination phase was far longer than those of ester type agents. Extents of brain uptake (brain-to-plasma partition coefficient, Kp value) of these drugs were determined at 3 different steady-state plasma concentrations (1 -15 μm). The Kp value of each drug was similar under the three different steady-state plasma concentrations. The Kp value increased in the following order; procaine (1.1) < PABA-Et(1.9) < lidocaine (2.2) < PABA-Pr (2.7)