Bupivacaine disposition and pharmacologic effects after intravenous and epidural administrations in dogs

Pharmacokinetic variables of bupivacaine (BPV) were determined after IV and epidural administrations in the same 6 dogs. Plasma BPV concentration curves after IV administration were adjusted to biexponential kinetics: a rapid distribution phase was followed by a slower elimination phase, with half-life of 34.5 +/- 7.8 minutes. Mean plasma clearance was 20.2 +/- 7.4 ml/min/kg of body weight, and mean volume of distribution at steady state was 0.7 +/- 0.2 L/kg. After epidural administration, absorption was rapid. Peak plasma concentration, 1.4 +/- 0.4 microgram/ml, was detected approximately 5 minutes after BPV administration. The half-life corresponding to epidural administration (179 +/- 33.6 minutes) was 5 to 6 times longer than that observed after IV administration, possibly because of the slow release of BPV from the epidural space. Induction times were short (2.3 +/- 2.2 minutes); anesthesia quickly began and lasted for more than 2 hours (158 +/- 48.8 minutes). During that period, BPV plasma concentration ranged between 1.4 and 0.2 microgram/ml. Changes in systolic blood pressure and heart rate were correlated to high plasma concentration of BPV. These modifications were observed for the first 30 minutes, reaching baseline values after 60 minutes.