caa a22 4500 475818237 CHVBK 20180406123815.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s002280050720 doi (NATIONALLICENCE)springer-10.1007/s002280050720 The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone [Elektronische Daten] [T. Varis, K. T. Kivistö, P. J. Neuvonen] Objective: To examine the possible effect of itraconazole on the pharmacokinetics and pharmacodynamics of orally administered prednisolone. Methods: In this double-blind, randomised, two-phase cross-over study, ten healthy subjects received either 200 mg itraconazole or placebo orally once a day for 4 days. On day 4, 20 mg prednisolone was given orally. Plasma concentrations of prednisolone, cortisol, itraconazole, and hydroxyitraconazole were determined by means of high-performance liquid chromatography up to 47 h. Results: Itraconazole increased the total area under the plasma prednisolone concentration-time curve by 24% (P < 0.001) and the elimination half-life of prednisolone by 29% (P < 0.001) compared with placebo. The peak plasma concentration and time to the peak of prednisolone were not affected by itraconazole. The mean morning plasma cortisol concentration, measured 23 h after the ingestion of prednisolone, during the itraconazole phase was 73% of that during the placebo phase (P < 0.001). Conclusions: The observed minor interaction between itraconazole and oral prednisolone is probably of limited clinical significance. The susceptibility of prednisolone to interact with CYP3A4 inhibitors is considerably smaller than that of methylprednisolone, and itraconazole and probably also other inhibitors of CYP3A4 can be used concomitantly with prednisolone without marked changes in the effects of this corticosteroid. Springer-Verlag Berlin Heidelberg, 2000 Key words Prednisolone nationallicence Itraconazole nationallicence Interaction nationallicence Varis T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Kivistö K. T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Neuvonen P. J. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut https://doi.org/10.1007/s002280050720 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050720 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Varis T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut NATIONALLICENCE 700 1- Kivistö K. T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut NATIONALLICENCE 700 1- Neuvonen P. J. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer