Prediction of the effect of voriconazole on the pharmacokinetics of non-steroidal anti-inflammatory drugs.

To evaluate the impact of voriconazole on the pharmacokinetics of Non-steroidal anti-inflammatory drugs (NSAIDs). Pharmacokinetic and physiochemical properties of voriconazole and NSAIDs are applied to build physiologically based pharmacokinetic (PBPK) models using GastroplusTM . The PBPK models of voriconazole and NSAIDs are verified by published studies, respectively. After the successful verification, DDI simulations are applied to predict the effect of voriconazole on the pharmacokinetics of NSAIDs. The area under the plasma concentration-time curves extrapolated to infinity (AUC0-inf ) of celecoxib, ibuprofen, tenoxicam and piroxicam are increased by 51%, 7%, 2% and 1% in concurrent use with voriconazole, respectively. The maximum concentration (Cmax ) of celecoxib, ibuprofen, tenoxicam and piroxicam are increased by 21%, 1%, 1% and 1% in the presence of concomitant voriconazole, respectively. Considering the inter-patient variability, changes in AUC or Cmax are not clinically meaningful. Therefore, adverse events and toxicity that are associated with celecoxib should be closely monitored when in combination with voriconazole, and this result can provide guidance for clinical DDI studies.