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

Published online by Cambridge University Press:  23 December 2004

M. J. G. Simon ,
B. T. Veering ,
R. Stienstra ,
J. W. van Kleef ,
S. G. P. Williams ,
G. M. McGuire  and
A. G. L. Burm
M. J. G. Simon
Affiliation:
Leiden University Medical Centre, Department of Anaesthesiology, Leiden, The Netherlands
B. T. Veering
Affiliation:
Leiden University Medical Centre, Department of Anaesthesiology, Leiden, The Netherlands
R. Stienstra
Affiliation:
Leiden University Medical Centre, Department of Anaesthesiology, Leiden, The Netherlands
J. W. van Kleef
Affiliation:
Leiden University Medical Centre, Department of Anaesthesiology, Leiden, The Netherlands
S. G. P. Williams
Affiliation:
Inveresk Research International Ltd, Tranent, Scotland, UK
G. M. McGuire
Affiliation:
Inveresk Research International Ltd, Tranent, Scotland, UK
A. G. L. Burm
Affiliation:
Leiden University Medical Centre, Department of Anaesthesiology, Leiden, The Netherlands
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Abstract

Summary

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 ± 14 L), 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.

Keywords

ANAESTHETIC TECHNIQUES, epiduralANAESTHETICS, LOCAL, levobupivacaineHUMAN EXPERIMENTATIONPHARMACOKINETICS, levobupivacaine
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 21 , Issue 6 , June 2004 , pp. 460 - 470
Copyright
2004 European Society of Anaesthesiology

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