You could be reading the full-text of this article now if you...

If you have access to this article through your institution,
you can view this article in

The systemic absorption and disposition of levobupivacaine 0.5% after epidural administration in surgical patients: a stable-isotope study

Simon, M. J. G.*; Veering, B. T.*; Stienstra, R.*; van Kleef, J. W.*; Williams, S. G. P.; McGuire, G. M.; Burm, A. G. L.*

European Journal of Anaesthesiology:
Original Article
Abstract

Background and objective: Absorption and disposition kinetics can be studied with a stable-isotope method. The aim of this study was to validate a stable-isotope method for levobupivacaine and to derive the relevant pharmacokinetics after epidural administration.

Methods: Eight volunteers (18-32 yr) received approximately 23 mg of both levobupivacaine and deuterium-labelled levobupivacaine simultaneously by intravenous infusion. Venous blood samples were taken for 8 h. Fifteen patients (23-85 yr) received 19 mL levobupivacaine 0.5% (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected for 24 h. Plasma concentrations were determined using liquid chromatography-mass spectrometry. Plasma concentration-time data were analysed by compartmental and non-compartmental analysis.

Results: Based on the ratio of the normalized areas under the curve of unlabelled and deuterium-labelled levobupivacaine in volunteers, as determined by both compartmental (mean ratio: 1.02, 90% CI: 1.00-1.04) and non-compartmental analysis (mean ratio: 1.02, 90% CI: 1.00-1.03) the two formulations were considered equivalent. In surgical patients the elimination half-life (mean ± SD: 196 ± 65 min), total body clearance (349 ± 114 mL min−1) and volume of distribution at steady state (56 ± 14L), derived by compartmental analysis, were similar to those obtained by non-compartmental analysis. The absorption was bi-phasic. The fraction absorbed and half-life of the fast absorption process were 0.22 ± 0.06 and 5.2 ± 2.7 min, respectively. The values for the slow absorption process were 0.84 ± 0.14 and 386 ± 91 min, respectively.

Conclusions: D3-levobupivacaine is pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to study the absorption and disposition kinetics after perineural administration of levobupivacaine in a single experiment.

Author Information

*Leiden University Medical Centre, Department of Anaesthesiology, Leiden, The Netherlands; Inveresk Research International Ltd, Tranent, Scotland, UK

Correspondence to: Mischa Simon, Department of Anaesthesiology (P-5), Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: M.J.G.Simon@lumc.nl; Tel: +31 71 526 2301; Fax: +31 71 524 8230

Accepted for publication August 2003 EJA 1553

© 2004 European Academy of Anaesthesiology