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Anesth Analg 2008; 106:143-146
© 2008 International Anesthesia Research Society
doi: 10.1213/01.ane.0000297293.84075.74
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ANESTHETIC PHARMACOLOGY

The Effect of a Long–Term Epidural Infusion of Ropivacaine on CYP2D6 Activity

Jeroen Wink, MD*, Bernadette Th. Veering, MD, PhD*, Michel Kruit, MD{ddagger}, Anton G. L. Burm, PhD*{dagger}, Gunilla A. I. Huledal, MSc Pharm§, Gunilla Y. Ekström, MD, PhD§, Rudolf Stienstra, MD, PhD*, and Jack W. van Kleef, MD, PhD*

From the *Department of Anesthesiology, Leiden University Medical Centre, Leiden, The Netherlands; {ddagger}Department of Anesthesiology, Rijnland Hospital, Leiderdorp, The Netherlands; and §AstraZeneca R&D, Södertälje, Sweden.

Address correspondence to Jeroen Wink, MD, Department of Anesthesiology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. Address e-mail to j.wink{at}lumc.nl.

BACKGROUND: Ropivacaine and one of its metabolites, pipecoloxylidide, inhibit CYP2D6 in. human liver microsomes in vitro with Ki values of 5 µM (1.4 mg/L) and 13 µM (3.6 mg/L), respectively.

We investigated the effect of a 50 h continuous epidural infusion of ropivacaine 2 mg/mL at a rate of 14 mL/h on CYP2D6 activity.

METHODS: Nineteen patients (41–85 yr) undergoing hip or knee replacement, all extensive metabolizers with respect to CYP2D6 activity, were included. Medications known to inhibit or be metabolized by CYP2D6, or known to be strong inhibitors/inducers of CYP1A2 or CYP3A4 were not allowed. Patients received 10 mg debrisoquine (a marker for CYP2D6 activity) before surgery and after 40 h epidural infusion. The metabolic ratio (MR) for debrisoquine hydroxylation was calculated as the amount of debrisoquine/amount of 4-OH-debrisoquine excreted in 0–10 h urine.

RESULTS: The median (range) of MR before and after ropivacaine were 0.54 (0.1–3.4) and 1.79 (0.3–6.7), respectively. The Hodges Lehman estimate of the ratio MR after/MR before ropivacaine was 2.2 with a 95% confidence interval 1.9–2.7 (P < 0.001).

CONCLUSION: A continuous epidural infusion of ropivacaine inhibits CYP2D6 activity in patients who are extensive metabolizers resulting in a twofold increase in the MR for debrisoquine hydroxylation. However, since none of the patients was converted into a functional poor metabolizer (MR >12.6), the effect on the metabolism of other drugs metabolized by CYP2D6 is unlikely to be of major clinical importance.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2008 by the International Anesthesia Research Society.