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

We studied seven healthy volunteers given itraconazole 200 mg orally or pla cebo, once daily for 4 days, in a crossover study. On day 4, racemic bupiva caine 0.3 mg kg(-1) was given i.v. over 60 min and venous plasma samples we re collected for 23 h. Plasma concentrations of R- and S-bupivacaine, itrac onazole and hydroxyitraconazole were measured. Itraconazole reduced the cle arance 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 variabl es of the enantiomers. Reduction of bupivacaine clearance by itraconazole p robably increases the steady-state concentration of bupivacaine enantiomers by 20-25%. This should be taken into account in the concomitant use of bup ivacaine and itraconazole, although the interaction seems to be of limited clinical significance.