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Pharmacokinetics of intraperitoneal and subcutaneous levobupivacaine in anesthetized rats

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Abstract

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

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Acknowledgements

We would like to express our appreciation to the staff of the animal experiment facilities of Hiroshima University for their kind assistance. We also express our appreciation to the Maruishi Pharmaceutical Co., Ltd. for the measurement of the blood concentration of levobupivacaine.

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The authors have no sources of funding to declare for this manuscript.

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Authors and Affiliations

  1. Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Hirotsugu Miyoshi, Takahiro Kato, Ryuji Nakamura, Noboru Saeki, Yuko Noda, Satoshi Kamiya, Atsushi Morio & Yasuo M. Tsutsumi

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  1. Hirotsugu Miyoshi
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  2. Takahiro Kato
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  3. Ryuji Nakamura
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  4. Noboru Saeki
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  5. Yuko Noda
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  6. Satoshi Kamiya
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  7. Atsushi Morio
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  8. Yasuo M. Tsutsumi
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Correspondence to Hirotsugu Miyoshi.

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Miyoshi, H., Kato, T., Nakamura, R. et al. Pharmacokinetics of intraperitoneal and subcutaneous levobupivacaine in anesthetized rats. J Anesth 35, 168–174 (2021). https://doi.org/10.1007/s00540-020-02883-8

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  • DOI: https://doi.org/10.1007/s00540-020-02883-8

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