Pharmacokinetics of intraperitoneal and subcutaneous levobupivacaine in anesthetized rats.

Abstract

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. Thirty-two rats were anesthetized with sevoflurane. In Experiment 1, we administered 5.0mg/kg of levobupivacaine intraperitoneally (IP) (n = 7), subcutaneously (SC) (n = 6), or intravenously (IV) (n = 6). In Experiment 2, we administered 2.5mg/kg of levobupivacaine IP (n = 7) or SC (n = 6). Data are shown as median [range] of Experiment 1. 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 120min 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]mgh/L; SC: 0.78 [0.39-0.98]mgh/L; P = 0.04). Levobupivacaine is rapidly absorbed following IP administration, but its maximum plasma concentration within 2h following IP administration is no statistical difference as that following SC administration. On the other hand, when levobupivacaine is given subcutaneously, Tmax can exceed 1h, so we need to be aware of local anesthetic toxicity during this period.