CHROMOPHARMACOLOGY - THE EFFICACY OF BUPI VACAINE FOR BLOCKING NERVE-CONDUCTION DOES NOT DEPEND ON TIME OF DAY

To test the hypothesis that the efficacy of local anaesthetics to bloc k nerve conduction is related the time of day (TOD) of drug applicatio n,we retrospectively analysed data from previous experiments on tachyp hylaxis. During the course of these experiments, as a measure of drug efficacy we determined the minimal blocking concentration (c(m)) of bu pivacaine in rabbit aortic nerves at several TODs. The special in situ preparation used permitted study of local anaesthetic pharmacodynamic s without the influence of pharmacokinetics, making it possible to inv estigate the chronopharmacodynamics of these drugs by relating c(m)s t o the respective TODs of their measurement. Methods: In 43 New Zealand rabbits anaesthetised with urethane, the aortic nerve was dissected a nd partly placed in a double-lumen perfusion chamber (Fig. 1A),which w as continuously perifused with tyrode solution or bupivacaine. Spike a ctivity was continuously recorded by bipolar platinum-iridium electrod es caudad to the chamber for control and cephalad for registration of blocking effects. As a measure of drug efficacy, by increasing the bup ivacaine concentration stepwise we determined the smallest concentrati on that blocks spike activity, i.e., c(m). After each determination bu pivacaine was rinsed off to confirm intact nerve function (Fig. 1B). R esults: Forty-nine determinations of bupivacaine c(m) were performed b etween 12:25 p.m. and 2:35 a.m. Data were pooled into groups of 2 h (F ig. 2). There was no significant difference between groups (ANOVA). In particular, c(m) at 3:00 p.m. was not lower than at 11:00 p.m., times at which local anaesthetics have been found to be most and least effe ctive, respectively. Conclusions: The c(m) of bupivacaine, and thus it s efficacy to block nerve conduction, does not depend on TOD of drug a pplication. Therefore, it is suggested that chronopharmacodynamics doe s not play an important role in the well-known circadian rhythm of the action of bupivacaine and probably of local anaesthetics in general.