Study on brain uptake of local anesthetics in rats.
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 microM). 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) less than PABA-Et (1.9) less than lidocaine (2.2) less than PABA-Pr (2.7) less than PABA-Bu (3.6). A linear relationship was observed between the Kp value and the logarithmic value of the partition coefficient obtained in n-heptane/water or n-octanol/water partition system. The value of PABA-Et and PABA-Bu following intravenous bolus administration were varied with time elapsed but the mean values were almost same with those obtained under steady-state plasma conditions.
Nakazono
T
T
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Murakami
T
T
Higashi
Y
Y
Yata
N
N
D010129:4-Aminobenzoic Acid / Q000097:blood; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D004952:Esters / Q000097:blood; D008012:Lidocaine / Q000097:blood; D008297:Male; D011343:Procaine / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D062366:para-Aminobenzoates
D000779:Anesthetics, Local; D004952:Esters; D062366:para-Aminobenzoates; D011343:Procaine; D008012:Lidocaine; D010129:4-Aminobenzoic Acid