caa a22 4500 477055893 CHVBK 20180405111346.0 cr unu---uuuuu 170330e19961201xx s 000 0 eng 10.1007/s002280050207 doi (NATIONALLICENCE)springer-10.1007/s002280050207 Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone [Elektronische Daten] [K.-M. Jalava, K. T. Olkkola, P. J. Neuvonen] Objective: We studied the possible interaction between itraconazole, a potent inhibitor of CYP3A, and zopiclone, a short-acting hypnotic. Methods: A double-blind, randomized, two-phase crossover design was used. Ten healthy young subjects received daily either 200 mg itraconazole or placebo for 4 days. On day 4 they ingested a single 7.5-mg oral dose of zopiclone. Plasma concentrations of zopiclone and itraconazole were determined and pharmacodynamic responses were measured up to 17 h. Results: Itraconazole significantly increased the Cmax of zopiclone from 49 to 63 ng ⋅ ml−1. The t1/2 of zopiclone was prolonged from 5.0 to 7.0 h. The AUC(0-∞) of zopiclone was increased from 415 to 719 ng ⋅ ml−1 h by itraconazole. No statistically significant differences were observed in the pharmacodynamic responses between the groups. Conclusion: Itraconazole has a statistically significant pharmacokinetic interaction with zopiclone but this is only of limited clinical importance, at least in young adults. Springer-Verlag Berlin Heidelberg, 1996 Key words Zopiclone nationallicence Itraconazole nationallicence drug interaction nationallicence pharmacokinetics nationallicence pharmacodynamics nationallicence Jalava K.-M Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland, FI aut Olkkola K. T. Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland, FI aut Neuvonen P. J. Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland, FI aut https://doi.org/10.1007/s002280050207 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050207 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jalava K.-M Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland, FI aut NATIONALLICENCE 700 1- Olkkola K. T. Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland, FI aut NATIONALLICENCE 700 1- Neuvonen P. J. Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland, FI aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer