caa a22 4500 475818512 CHVBK 20180406123816.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/s002280000171 doi (NATIONALLICENCE)springer-10.1007/s002280000171 Grapefruit juice can increase the plasma concentrations of oral methylprednisolone [Elektronische Daten] [T. Varis, K. T. Kivistö, P. J. Neuvonen] Objective: To investigate whether the pharmacokinetics of orally administered methylprednisolone and plasma cortisol concentrations are affected by administration of grapefruit juice. Methods: In a randomised, two-phase, cross-over study, ten healthy subjects received either 200 ml double-strength grapefruit juice or water three times a day for 2 days. On day 3, 16 mg methylprednisolone was given orally with 200 ml grapefruit juice or water. Additionally, 200 ml grapefruit juice or water was ingested 0.5 h and 1.5 h after methylprednisolone administration. Plasma concentrations of methylprednisolone and cortisol were determined using liquid chromatography/mass spectrometry (LC/MS/MS) over a 47-h period. Results: Grapefruit juice increased the total area under the plasma methylprednisolone concentration-time curve (AUC0-∞) by 75% (P < 0.001) and the elimination half-life (t 1/2) of methylprednisolone by 35% (P < 0.001). The peak plasma concentration of methylprednisolone (Cmax) was increased by 27% (P < 0.01). Grapefruit juice delayed the time to the Cmax from 2.0 h to 3.0 h (P < 0.05). There was no significant difference in the plasma cortisol concentrations, measured after methylprednisolone administration, between the water and grapefruit juice phases. However, grapefruit juice slightly decreased the morning plasma cortisol concentrations before methylprednisolone administration (P < 0.05). Conclusions: Grapefruit juice given in high amounts moderately increases the AUC0-∞ and t 1/2 of oral methylprednisolone. The increase in t 1/2 suggests that grapefruit juice can affect the systemic methylprednisolone metabolism. The clinical significance of the grapefruit juice-methylprednisolone interaction is small, but in some sensitive subjects high doses of grapefruit juice might enhance the effects of oral methylprednisolone. Springer-Verlag Berlin Heidelberg, 2000 Key words Methylprednisolone nationallicence Grapefruit juice 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@hus.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@hus.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@hus.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut https://doi.org/10.1007/s002280000171 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000171 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@hus.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@hus.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@hus.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