Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects

Aims To assess the effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem. Methods In a randomized cross‐over study with two phases, 10 healthy subjects ingested 10 mg of zolpidem with or without oral voriconazole pretreatment. The concentrations of zolpidem were measured in plasma up to 24 h and pharmacodynamic variables were monitored for 12 h. Results Voriconazole increased the peak plasma concentration of zolpidem by 1.23‐fold [ P  < 0.05; 90% confidence interval (CI) 1.05, 1.45] and the area under the plasma zolpidem concentration–time curve by 1.48‐fold ( P  < 0.001; 90% CI 1.29, 1.74). The time to peak plasma zolpidem concentration was unchanged by voriconazole but the half‐life was prolonged from 3.2 to 4.1 h ( P  < 0.01; 95% CI on the difference 0.27, 1.45). The pharmacodynamics of zolpidem were unaffected by voriconazole. Conclusion Voriconazole caused a moderate increase in exposure to zolpidem in healthy young subjects but no clear pharmacodynamic changes were observed between the groups.