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British Journal of Anaesthesia, Vol 83, Issue 4 659-661, Copyright © 1999 by The Board of Management and Trustees of the British Journal of Anaesthesia

SHORT COMMUNICATIONS

Effect of itraconazole on the pharmacokinetics of bupivacaine enantiomers in healthy volunteers

V. J. Palkama, P. J. Neuvonen and K. T. Olkkola
Department of Anaesthesia and Department of Clinical Pharmacology, University of Helsinki, PO Box 260, FIN-00029 Hyks, Finland

We studied seven healthy volunteers given itraconazole 200 mg orally or placebo, once daily for 4 days, in a crossover study. On day 4, racemic bupivacaine 0.3 mg kg-1 was given i.v. over 60 min and venous plasma samples were collected for 23 h. Plasma concentrations of R- and S- bupivacaine, itraconazole and hydroxyitraconazole were measured. Itraconazole reduced the clearance of R-bupivacaine by 21% (P < 0.05) and that of S-bupivacaine by 25% (P < 0.05), while it had no significant effect on other pharmacokinetic variables of the enantiomers. Reduction of bupivacaine clearance by itraconazole probably increases the steady-state concentration of bupivacaine enantiomers by 20-25%. This should be taken into account in the concomitant use of bupivacaine and itraconazole, although the interaction seems to be of limited clinical significance.
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