Effect of itraconazole on the pharmacokinetics of inhaled lidocaine

Abstract

Lidocaine is metabolized by cytochrome P450 3A4 and 1A2 enzymes (CYP3A4 and CYP1A2) in vitro. However, their relative contribution to the elimination of lidocaine depends on lidocaine concentration. We have studied the effect of a potent CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of inhaled lidocaine in ten healthy volunteers using a randomized, two-phase cross-over study design. The interval between the phases was four weeks. The subjects were given orally itraconazole (200 mg once a day) or placebo for four days. On day 4, each subject inhaled a single dose of 1.5 mg/kg of lidocaine by nebulizer. Plasma samples were collected until 10 hr and the concentrations of lidocaine and its major metabolite monoethylglycinexylidide were measured by gas chromatography. The areas under the lidocaine and monoethylglycinexylidide concentration time curves were similar during both phases. No statistically significant differences were observed in any of the pharmacokinetic parameters; peak concentrations, concentration peak times or elimination half-lives of lidocaine or monoethylglycinexylidide. The clinical implication of this study is that no lidocaine dosage adjustments are necessary if it is used to prepare the airway prior to endoscopic procedures or intubation in patients using itraconazole or other inhibitors of CYP3A4.