Effect of aprepitant on etoposide pharmacokinetics in patients with testicular cancer: a pharmacokinetic study to determine the absence of a clinically relevant interaction.

All patients treated with anticancer agents should receive the most effective antiemetic regimen. Antiemetic guidelines provide recommendations but do not take into account possible drug-drug interactions between anti-emetics and anticancer drugs. This study determines the clinical relevance of the potential drug-drug interaction of the neurokinin-1 receptor antagonist, aprepitant, on the pharmacokinetics of etoposide. Aprepitant is a moderate CYP3A4 inhibitor and may increase the systemic exposure of etoposide which is partly metabolized by cytochrome P450 enzyme 3A4 (CYP3A4). In this prospective observational study the pharmacokinetics of etoposide with and without concomitant use of aprepitant was determined in 12 patients receiving first-line chemotherapy for testicular cancer. The geometric mean (95% confidence interval) area under the plasma concentration-time curve 0-24h (AUC 0-24h ) of etoposide with aprepitant was 86.2 (79.7-93.2) mg/l*h vs. 83.7 (75.8 - 92.4) mg/l*h without aprepitant. Geometric mean ratios (90% confidence intervals) of AUC 0-24h and maximum plasma concentration (C max ) for etoposide with and without aprepitant were 1.03 (0.96-1.10) and 0.96 (0.89 - 1.03), respectively. This study confirms the absence of a clinical relevant interaction between etoposide and aprepitant. Both drugs can be safely combined without affecting etoposide exposure.