Temporal changes in bupivacaine kinetics.

The chronokinetics of bupivacaine have been examined in the mouse. Different groups of adult male NMRI mice maintained under controlled environmental conditions received a single intraperitoneal injection of bupivacaine (20 mg kg-1) at one of four different fixed time points in a 24 h period i.e. 10:00, 16:00, 22:00 and 04:00 h. Blood samples were taken 0.25, 0.5, 0.75, 1, 1.5, 3, 4 and 6 h after drug administration and total serum levels of bupivacaine were determined by a gas-liquid chromatography with a flame ionization detector. Statistically significant temporal changes were found in the following pharmacokinetic parameters: highest Cmax value = 0.900 +/- 0.080 micrograms mL-1 at 22:00 h (amplitude, maximum-minimum/mean X 100, is 64%); highest Cmax/Tmax ratio = 3.596 +/- 0.339 at 22:00 h (amplitude = 85%); highest beta elimination half-life, T1/2 beta, = 3.950 +/- 0.246 h at 22:00 h (amplitude = 35%); area under concentration curve (AUC infinity 0) was not found to be significantly different among the hours of administration. The temporal kinetic changes demonstrated suggest a possible circadian difference in bupivacaine efficacy and/or toxicity.