Acta anaesthesiologica Scandinavica
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Acta Anaesthesiol Scand · Nov 2008
Randomized Controlled TrialItraconazole, a potent inhibitor of P-glycoprotein, moderately increases plasma concentrations of oral morphine.
Individual variation in opioid response is considerable, partly due to pharmacokinetic factors. Transporter proteins are becoming increasingly interesting also in the pharmacokinetics of opioids. The efflux transporter P-glycoprotein can affect gastrointestinal absorption and tissue distribution, particularly brain access of many opioids. The aim of this study was to evaluate whether itraconazole, which is a potent inhibitor of P-glycoprotein and CYP3A4, would change the pharmacokinetics or the pharmacodynamics of oral morphine. ⋯ Itraconazole moderately increases plasma concentrations of oral morphine, probably by enhancing its absorption by inhibiting intestinal wall P-glycoprotein. A possible improvement of morphine penetration to the brain could not be observed.