Pharmacokinetics and pharmacologic effects of the S(-) isomer of bupivacaine after intravenous and epidural administration in dogs

Objective-To determine pharmacokinetic variables and pharmacologic effects of the S(-) isomer of bupivacaine (S[-]-BPV) in dogs. Animals-6 adult male Beagles. Procedure-Dogs received S(-)-BPV(1 mg/kg of body weight) IV, and 15 days la ter, the same dogs received 1.8 mg/kg epidurally. Pharmacokinetic variables and pharmacologic effects were determined for each route of administration . Results-After IV administration, plasma concentration versus time curves we re adjusted, using biexponential equations that indicated a rapid distribut ion phase followed by a slower elimination phase, with a mean +/- SD half-l ife of 33.5 +/- 17.0 minutes. Mean plasma clearance was 21.0 +/- 10.7 ml/mi n/kg, and mean volume of distribution at steady slate was 0.8 +/- 0.2 L/kg. After IV administration, mean peak plasma concentration was 2.6 +/- 0.7 mu g/ml; after epidural administration, it was 0.9 +/- 0.5 mu g/ml at approxi mately 3 minutes. Half-life after epidural administration was 5 times longe r than that observed after IV administration. Motor block began immediately after the end of epidural administration and lasted for 3 to 4 hours. Chan ges in systolic blood pressure and heart rate after epidural administration were slight but occurred at the same lime that plasma concentration peaked . After IV administration, motor block or variations in physiologic variabl es studied were not observed. Conclusions and Clinical Relevance-In dogs, the pharmacologic behavior of S (-)-BPV was similar to that of the bupivacaine racemate, but motor block at tributable to S(-)-BPV lasted longer than that attributable to the racemate , with lower plasma concentrations observed at equivalent sample collection times.