Influence of aprepitant and localization of the patch on fentanyl exposure in patients with cancer using transdermal fentanyl.

Abstract

Background and ObjectivesThe cutaneous fentanyl patch is widely used to treat continuous pain in patients with cancer. Its use is hampered by a high inter- and intrapatient pharmacokinetic variability. Factors that influence this pharmacokinetic variability are largely unclear. The aim of these studies was to test if common patient variables, i) the use of the moderate CYP3A4 inhibitor aprepitant and ii) the localization of the fentanyl patch (upper arm versus thorax) influence systemic exposure to fentanyl in patients with cancer using a transdermal fentanyl patch.ResultsThe AUC0–6 h of fentanyl was 7.1% (95% CI: −28% to +19%) lower if patients concurrently used aprepitant, compared to the period when patients used fentanyl only. The AUC0–4 h of fentanyl was 7.4% (95% CI: −22% to +49%) higher when the cutaneous fentanyl patch was applied to the upper arm compared to application at the thorax.ConclusionsNeither the concurrent use of aprepitant, nor the localization of the fentanyl patch showed a statistically significant influence on fentanyl pharmacokinetics.MethodsWe performed two prospective cross-over pharmacokinetic intervention studies. Both studies had two eight-day study periods. At day 8 of each study period blood samples were collected for pharmacokinetic analysis. In each study 14 evaluable patients were included.