Pharmacokinetics of intraperitoneal and subcutaneous levobupivacaine in anesthetized rats

• Published in: Journal of anesthesia 2021-04, Vol.35 (2), p.168-174, Article 168
• Main Authors: Miyoshi, Hirotsugu, Kato, Takahiro, Nakamura, Ryuji, Saeki, Noboru, Noda, Yuko, Kamiya, Satoshi, Morio, Atsushi, Tsutsumi, Yasuo M.
• Format: Article
• Language: English
• Subjects: Anesthesiology; Anesthetics, Local - toxicity; Animal experimentation; Animals; Bupivacaine - toxicity; Comparative analysis; Critical Care Medicine; Emergency Medicine; Intensive; Levobupivacaine; Medicine; Medicine & Public Health; Original Article; Pain Medicine; Rats; Sevoflurane
• ISSN: 0913-8668; 1438-8359
• DOI: 10.1007/s00540-020-02883-8

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 max can exceed 1 h, so we need to be aware of local anesthetic toxicity during this period.