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Effect of propofol on ropivacaine metabolism in human liver microsomes

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Abstract

A combination of the general anesthestic propofol and epidural anesthesia with a local anesthetic is widely used. The metabolism of ropivacaine and that of lidocaine are mediated by similar P450 isoforms. Previously, propofol was found to inhibit the metabolism of lidocaine in vitro. Here we investigated whether propofol inhibits the metabolism of ropivacaine using human liver microsomes in vitro. Ropivacaine (6.0 µmol·l−1) as the substrate and propofol (1–100 µmol·l−1) were reacted together using human microsomes. The concentrations of ropivacaine and its major metabolite 2′,6′-pipecoloxylidide (PPX) were measured using high-performance liquid chromatography. The metabolic activity of ropivacaine was reflected in the production of PPX. The inhibitory effects of propofol on ropivacaine metabolism were observed to be dose-dependent. The IC50 of propofol was 34.9 µmol·l−1. Propofol shows a competitive inhibitory effect on the metabolism of ropivacaine (i.e., PPX production mediated by CYP3A4) in human CYP systems in vitro.

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Authors and Affiliations

  1. Graduate School, University of Tsukuba, Tsukuba, Japan

    Yoshiko Osaka

  2. Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan

    Shinichi Inomata, Masayuki Miyabe, Hidenori Toyooka & Makoto Tanaka

  3. Department of Legal Medicine, University of Tsukuba, Tsukuba, Japan

    Einosuke Tanaka, Takako Nakamura & Katsuya Honda

Authors
  1. Yoshiko Osaka
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  2. Shinichi Inomata
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  3. Einosuke Tanaka
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  4. Takako Nakamura
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  5. Katsuya Honda
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  6. Masayuki Miyabe
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  7. Hidenori Toyooka
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  8. Makoto Tanaka
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Osaka, Y., Inomata, S., Tanaka, E. et al. Effect of propofol on ropivacaine metabolism in human liver microsomes. J Anesth 20, 60–63 (2006). https://doi.org/10.1007/s00540-005-0358-5

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  • DOI: https://doi.org/10.1007/s00540-005-0358-5

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