title: Effect of itraconazole on the pharmacokinetics of bupivacaine enantiomers in healthy volunteers.
abstract: 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.
authors.affiliation: Department of Anaesthesia, University of Helsinki, Hyks, Finland.
authors.forename: V J
authors.initials: VJ
authors.lastname: Palkama
authors.forename: P J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: K T
authors.initials: KT
authors.lastname: Olkkola
mesh_terms: D000328:Adult; D000779:Anesthetics, Local / Q000097:blood*; D000935:Antifungal Agents / Q000494:pharmacology*; D002045:Bupivacaine / Q000097:blood*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D013237:Stereoisomerism
chemical_list: D000779:Anesthetics, Local; D000935:Antifungal Agents; D017964:Itraconazole; D002045:Bupivacaine