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Research ArticleArticle

Cerebrospinal Fluid Bioavailability and Pharmacokinetics of Bupivacaine and Lidocaine after Intrathecal and Epidural Administrations in Rabbits Using Microdialysis

Rozenn Clement, Jean-Marc Malinovsky, Pascal Le Corre, Gilles Dollo, Francois Chevanne and Roger Le Verge
Journal of Pharmacology and Experimental Therapeutics May 1999, 289 (2) 1015-1021;
Rozenn Clement
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Jean-Marc Malinovsky
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Pascal Le Corre
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Gilles Dollo
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Francois Chevanne
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Roger Le Verge
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Abstract

The aim of this work was to study the cerebrospinal fluid (CSF) bioavailability and pharmacokinetics of bupivacaine (BUP) and lidocaine (LID) administered separately in rabbits using microdialysis with retrodialysis calibration. Microdialysis probe and catheters were inserted under control of the view in the intrathecal or epidural spaces. The epidural disposition of BUP and LID after epidural administration of low (0.69 μM) and high (6.9 μM) doses was studied. Then, the intrathecal and plasma dispositions after separate intrathecal (0.2 μM) and epidural administration (6.9 μM) were investigated. The CSF binding of BUP and LID was linear in a range from 50 to 500 μg/ml, and the mean unbound CSF fraction at a concentration of 100 μg/ml was 39.3 ± 2.3% for BUP and 75.8 ± 7.7% for LID. Epidural and intrathecal disposition of BUP and LID showed a biexponential decline. After epidural administration, the CSF concentrations of BUP and LID were much higher than those in plasma. After intrathecal administration, the plasma concentrations were below the limit of quantitation. Although the absorption rate of BUP appeared higher than that of LID, the mean CSF bioavailability of epidural BUP and LID was 5.5 and 17.7%, respectively. The unexpectedly higher CSF bioavailability of LID, the less lipophilic drug, may result from the difference in the processes competing for drug epidural removal.

Footnotes

  • Send reprint requests to: Dr. Pascal Le Corre, Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 35043 Rennes Cedex, France. E-mail:Pascal.le-corre{at}univ-rennes1.fr

  • Abbreviations:
    CSF
    cerebrospinal fluid
    BUP
    bupivacaine
    LID
    lidocaine
    RL
    relative loss
    RR
    relative recovery
    Cmax
    maximum total plasma concentration
    Cmax-epi
    maximum unbound epidural concentration
    Tmax
    peak plasma concentration time
    Tmax-csf
    peak CSF concentration time
    AUClast
    area under CSF concentration-time curves from the time of drug administration up to the last sampling point
    AUCcsf-it
    area under the unbound CSF concentration-time curve up to the last sampling point after intrathecal administration
    AUCcsf-epi
    area under the unbound CSF concentration-time curve up to the last sampling point after epidural administration
    AUCinf
    area under CSF concentration-time curves from the time of drug administration to infinity
    K10
    elimination rate constant
    K12 and K21
    distribution rate constants
    Ka
    absorption rate constant
    V1
    initial volume of distribution
    Vss
    steady-state volume of distribution
    Fcsf
    CSF bioavailability
    Cinj
    drug concentration of the solution injected
    CLE
    elimination clearance
    CLI
    intercompartmental clearance
    • Received July 10, 1998.
    • Accepted January 7, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 2
1 May 1999
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Research ArticleArticle

Cerebrospinal Fluid Bioavailability and Pharmacokinetics of Bupivacaine and Lidocaine after Intrathecal and Epidural Administrations in Rabbits Using Microdialysis

Rozenn Clement, Jean-Marc Malinovsky, Pascal Le Corre, Gilles Dollo, Francois Chevanne and Roger Le Verge
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 1015-1021;

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Research ArticleArticle

Cerebrospinal Fluid Bioavailability and Pharmacokinetics of Bupivacaine and Lidocaine after Intrathecal and Epidural Administrations in Rabbits Using Microdialysis

Rozenn Clement, Jean-Marc Malinovsky, Pascal Le Corre, Gilles Dollo, Francois Chevanne and Roger Le Verge
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 1015-1021;
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