Pharmacokinetics of lidocaine, bupivacaine, and levobupivacaine in plasma and brain in awake rats.

BACKGROUND We have compared the pharmacokinetics and brain distribution of lidocaine, racemic bupivacaine (bupivacaine), and levobupivacaine in awake, spontaneously breathing rats. METHODS Lidocaine (0.5 mg x kg x min), bupivacaine (0.1 mg x kg x min), or levobupivacaine (0.1 mg x kg x min) was continuously administered to rats for 2 h (n = 12, each anesthetic). Blood samples and cerebral dialysate were collected during infusion and for 2 h after termination of infusion. Concentrations of anesthetics in the cerebral extracellular fluid were measured by microdialysis using the retrodialysis calibration method. Tissue-to-plasma partition coefficients calculated from the total (protein-bound and unbound) and unbound concentrations in plasma and brain as well as pharmacokinetic parameters in plasma and cerebral extracellular fluid were compared among the three anesthetics. RESULTS There were no differences in plasma total or unbound concentrations between bupivacaine and levobupivacaine. Concentrations of bupivacaine in the cerebral extracellular fluid were significantly higher than levobupivacaine (P < 0.001). Despite no differences in the ratio of total brain concentration to total plasma concentration among the three anesthetics, the ratio of cerebral extracellular fluid concentration to plasma unbound fraction of bupivacaine was significantly higher than lidocaine and levobupivacaine (0.58 +/- 0.09, 0.47 +/- 0.18, and 0.40 +/- 0.09, respectively; P = 0.03 and 0.003, respectively). CONCLUSIONS Although the ratio of total brain concentration to total plasma concentrations of lidocaine, bupivacaine, and levobupivacaine was similar, concentration ratio of bupivacaine in the cerebral extracellular fluid to plasma unbound fraction was significantly higher than lidocaine and levobupivacaine.