caa a22 4500 47581827X CHVBK 20180406123815.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s002280000124 doi (NATIONALLICENCE)springer-10.1007/s002280000124 Pharmacokinetics and organ distribution of intravenous and oral methylene blue [Elektronische Daten] [C. Peter, D. Hongwan, A. Küpfer, B. H. Lauterburg] Objective: To determine the pharmacokinetics and organ distribution of i.v. and oral methylene blue, which is used to prevent ifosfamide-induced encephalopathy in oncology. Methods: The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after i.v. and oral administration of 100 mg methylene blue with and without mesna. The distribution of methylene blue in different tissues was measured in rats after intraduodenal and i.v. application. Results: The time course of methylene blue in whole blood after i.v. administration showed a multiphasic time course with an estimated terminal half-life of 5.25 h. Following oral administration, the area under the concentration-time curve was much lower (9 nmol/min/ml vs 137 nmol/min/ml). Co-administration of mesna, which could influence distribution by ion-pairing, did not alter the pharmacokinetics. The urinary excretion of methylene blue and its leucoform was only moderately higher after i.v. administration (18% vs 28% dose). Intraduodenal administration to rats resulted in higher concentrations in intestinal wall and liver but lower concentrations in whole blood and brain than i.v. methylene blue. Conclusions: Differences in organ distribution of methylene blue are mainly responsible for the different pharmacokinetics after oral and i.v. administration. If methylene blue acts in the liver, where ifosfamide is primarily activated to reactive and potentially toxic metabolites, oral and i.v. methylene blue are likely to be equally effective. However, if the site of action is the central nervous system, i.v. methylene blue which results in much higher concentrations in brain seems preferable. Springer-Verlag Berlin Heidelberg, 2000 Key words Methylene blue nationallicence Pharmacokinetics nationallicence Distribution nationallicence Peter C. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut Hongwan D. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut Küpfer A. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut Lauterburg B. H. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut https://doi.org/10.1007/s002280000124 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000124 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Peter C. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut NATIONALLICENCE 700 1- Hongwan D. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut NATIONALLICENCE 700 1- Küpfer A. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut NATIONALLICENCE 700 1- Lauterburg B. H. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland e-mail: bernhard.lauterburg@ikp.unibe.ch Tel.: +41-31-6323569; Fax: +41-31-6324997, CH aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer