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


CONCLUSIONS
Voriconazole caused a moderate increase in exposure to zolpidem in healthy young subjects but no clear pharmacodynamic changes were observed between the groups.
Saari
Teijo I
TI
Department of Anaesthesiology and Intensive Care and the Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland. teijo.saari@tyks.fi
Laine
Kari
K
Leino
Kari
K
Valtonen
Mika
M
Neuvonen
Pertti J
PJ
Olkkola
Klaus T
KT
D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole; D000077334:Zolpidem
D000935:Antifungal Agents; D006993:Hypnotics and Sedatives; D011725:Pyridines; D011743:Pyrimidines; D014230:Triazoles; D000077334:Zolpidem; D065819:Voriconazole