Pharmacokinetics of Levobupivacaine, Fentanyl, and Clonidine After Administration in Thoracic Paravertebral Analgesia

There is little knowledge of the pharmacokinetics of local anesthetics and adjunctive analgesics after paravertebral blockade. We evaluated the pharmacokinetics of low-dose levobupivacaine, fentanyl, and clonidine after paravertebral analgesia for breast surgery. Thirty-eight patients receiving paravertebral analgesia for breast surgery received a 19-mL paravertebral bolus of levobupivacaine 0.25% combined with a 1-mL volume of saline (group L, 13 patients), fentanyl 50 μg (group LF, 13 patients), or clonidine 150 μg (group LC, 12 patients) followed 1 hour later by infusion of levobupivacaine 0.1% (L), levobupivacaine 0.05% with fentanyl 4 μg/mL (LF), or levobupivacaine 0.05% with clonidine 3 μg/mL (LC), respectively. Plasma concentrations of study drugs were determined at intervals up to 24 hours after bolus injection. There was rapid absorption of levobupivacaine after bolus with mean (standard deviation) maximum plasma concentration (Cpmax) of 0.51(0.24) μg/mL in a median time to maximum concentration tCpmax of 15 minutes. Mean Cpmax fentanyl and clonidine after bolus were 0.62 (0.37) and 0.79 (0.23) ng/mL, in a median tCpmax of 15 and 22.5 minutes, respectively. Mean Cpmax levobupivacaine after infusion was 0.47 (0.41) μg/mL in a median tCpmax of 24 hours. There was progressive accumulation of fentanyl and clonidine at 24 hours with a mean Cpmax of 0.72 (0.33) and 1.74 (0.70) ng/mL, respectively. After paravertebral bolus and infusion administration, Cpmax levobupivacaine was within the safe range. Cpmax fentanyl and clonidine were less than the effective levels after IV administration, suggesting that their analgesic effect may be partly attributed to a peripheral mechanism of action.