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ANALGESIA

Epidural, Intrathecal Pharmacokinetics, and Intrathecal Bioavailability of Ropivacaine

François-Xavier Rose, PharmD^*, Jean-Pierre Estebe, MD, PhD, Maja Ratajczak, PharmD^*, Eric Wodey, MD, PhD, François Chevanne, BS^*, Gilles Dollo, PharmD, PhD^*, David Bec, BS^*, Jean-Marc Malinovsky, MD, PhD^*, Claude Ecoffey, MD, and Pascal Le Corre, PharmD, PhD^*

From the *Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, and Département d’Anesthésie 2, Université de Rennes 1, Rennes Cedex, France.

Address correspondence and reprint requests to Pascal Le Corre, PharmD, PhD, Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 35043 Rennes Cedex, France. Address e-mail to pascal.le-corre{at}univ-rennes1.fr.

Abstract

BACKGROUND: Ropivacaine is used by the epidural route for postoperative pain management with various neuraxial techniques. Given the widespread use of these techniques and the relative paucity of data on spinal disposition of local anesthetics, we evaluated through an experimental animal model, the spinal disposition of ropivacaine, allowing further studies of factors influencing their intrathecal bioavailability.

METHODS: Sheep received an IV bolus dose of ropivacaine (50 mg), and 1 wk after, an intrathecal dose of ropivacaine (20 mg) followed 3 h later by epidural ropivacaine (100 mg). A simultaneous microdialysis technique was used to measure epidural and intrathecal drug concentrations after both epidural and intrathecal administrations.

RESULTS: Absorption-time plots showed a large variability in the systemic absorption after both intrathecal and epidural administration, with an apparent faster systemic absorption after intrathecal administration. In the intrathecal space, the elimination clearance was around three-times higher than the distribution clearance. In the epidural space, the relative contribution of elimination and distribution to ropivacaine disposition was different, indicating a more pronounced influence of the distribution process. The intrathecal bioavailability after epidural administration was 11.1% ± 7.6%.

CONCLUSIONS: Using an animal model, we showed that drug dispositions in the intrathecal and epidural compartments are different, and that the intrathecal bioavailability of ropivacaine after epidural administration is low, and highly variable.

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