Pharmacokinetics of intraperitoneal and subcutaneous levobupivacaine in anesthetized rats.

Background: We compared the pharmacokinetics of levobupivacaine when administered intraperitoneally, subcutaneously, and intravenously in an anesthetized rat model, to estimate the toxicity risk of a local anesthetic when absorbed from the peritoneum.

Methods: Thirty-two rats were anesthetized with sevoflurane. In Experiment 1, we administered 5.0 mg/kg of levobupivacaine intraperitoneally (IP) (n = 7), subcutaneously (SC) (n = 6), or intravenously (IV) (n = 6). In Experiment 2, we administered 2.5 mg/kg of levobupivacaine IP (n = 7) or SC (n = 6). Data are shown as median [range] of Experiment 1.

Results: In either of experiments, the time to reach maximum plasma concentration of levobupivacaine was shorter in the IP group than in the SC group (IP: 2 [2-5] min; SC: 5 [2-10] min; P = 0.04), and the maximum concentration of levobupivacaine did not differ between the IP and SC groups (IP: 0.45 [0.05-0.67] µg/mL; SC: 0.47 [0.21-0.62] µg/mL; P = 0.90). The area under the curve from time 0 to 120 min after levobupivacaine administration was significantly higher in the SC group than in the IP group in both experiments (IP: 0.29 [0.10-0.54] mg h/L; SC: 0.78 [0.39-0.98] mg h/L; P = 0.04).

Conclusion: Levobupivacaine is rapidly absorbed following IP administration, but its maximum plasma concentration within 2 h following IP administration is no statistical difference as that following SC administration. On the other hand, when levobupivacaine is given subcutaneously, T can exceed 1 h, so we need to be aware of local anesthetic toxicity during this period.