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 later, 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 were adjusted, using biexponential equations that indicated a rapid distribution phase followed by a slower elimination phase, with a mean ± SD half-life of 33.5 ± 17.0 minutes. Mean plasma clearance was 21.0 ± 10.7 ml/min/kg, and mean volume of distribution at steady state was 0.8 ± 0.2 L/kg. After IV administration, mean peak plasma concentration was 2.6 ± 0.7 μg/ml; after epidural administration, it was 0.9 ± 0.5 μg/ml at approximately 3 minutes. Half-life after epidural administration was 5 times longer than that observed after IV administration. Motor block began immediately after the end of epidural administration and lasted for 3 to 4 hours. Changes in systolic blood pressure and heart rate after epidural administration were slight but occurred at the same time that plasma concentration peaked. After IV administration, motor block or variations in physiologic variables 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 attributable to S(-)-BPV lasted longer than that attributable to the racemate with lower plasma concentrations observed at equivalent sample collection times.