Effect of the hour of administration on the pharmacokinetics of lidocaine in the rat.

The aim of the present study was to investigate an eventual influence of the hour of administration on lidocaine kinetics in the rat. 280 Wistar AF-SPF adult male rats were used for this study and maintained under controlled environmental conditions (LD: 06.00-18.00) during the month of October. A single 50 mg X kg-1 dose of lidocaine was given by intramuscular route, at four different fixed time points of a 24 hour period (i.e.: 10.00, 16.00, 22.00 and 04.00) to 70 rats. Blood samples were taken at the following time points: 5, 15, 30 min., 1, 2, 4 and 6 hours after the drug administration. Lidocaine plasma levels (free and bound) were determinated according to a specific gas chromatographic method. The data showed circadian variations of pharmacokinetic parameters:--Elimination half-life: max. 2.12 +/- 0.05 h at 10.00, min. 1.50 +/- 0.03 h at 16. --Initial concentration: max. 5.05 +/- 0.65 micrograms X ml-1 at 16.00; min. 2.97 +/- 0.29 micrograms X ml-1 at 04.00.--Elimination constant rate: max. 0.4618 +/- 0.0094 h-1 at 16.00, min 0.3279 +/- 0.0079 h-1 at 10.00.--Area under curve (experimental): max. 11.11 +/- 1.07 micrograms X kg-1 X h-1 at 16.00, min. 7.45 +/- 0.84 micrograms X kg-1 X h-1 at 04.00.--Apparent volume of distribution: max. 16.67 +/- 1,67 L X kg-1 at 04.00, min. 9.75 +/- 1.04 L X kg-1 at 16.00. The lidocaine-free fraction varied with time and the protein binding of lidocaine showed a circadian variation.(ABSTRACT TRUNCATED AT 250 WORDS)