caa a22 4500 465812171 CHVBK 20180323112119.0 cr unu---uuuuu 170327e19900101xx s 000 0 eng 10.1007/BF03190123 doi (NATIONALLICENCE)springer-10.1007/BF03190123 Plasma levels and urinary excretion of lormetazepam in patients with liver cirrhosis and in healthy volunteers [Elektronische Daten] [M. Hildebrand, A. Hellstern, M. Hümpel, D. Hellenbrecht, R. Saller] Summary: Plasma levels and urinary excretion of lormetazepam (Noctamid ®-ampoules; 2 mg/10 ml) were studied after i.v. (0.015 mg/kg b.w.) and after p.o (0.03 mg/kg b.w.) administration of the drug to five patients with cirrhosis of the liver (C) and to five young male volunteers (N). The cirrhotic patients exhibited higher drug plasma levels (Cmax p.o.: 11-43 ng/ml [C] vs. 11-16 ng/ml [N]) and higher AUC0-24 values of the unchanged drug (i.v.: 66-102 ng.h/ml [C] vs. 54-72 ng.h/ml [N]; p.o.: 83-188 ng.h/ml [C] vs. 74-113 ngJi/ml [N]). The absolute bioavailability was increased in (he C-group with 57-134% vs. 52-84% [N]. The total plasma clearance of lormetazepam was 3 ml/min/kg in the C-group and 4 ml/min/kg in the N-group and thus within the range known for elderly and young male subjects. Conversely to the parent compound, the AUC-figures of its 3-OH-glucuronide were higher in the N-group (346-434 ng.h/ml) than in the C-group (149-371 ng.h/ml). In 24 h pooled urine samples of both groups, the glucuronide of lorazepam, the N-demethylated metabolite, accounted for approximately 5-14% of the dose fraction excreted as lormetazepam glucuronide. Apart from increased levels of the unchanged drug due to porto-systemic shunt and/or disease-dependent lower glucuronidation rate, the pharmacokinetics of lormetazepam were not altered in cirrhotic patients. It can therefore be concluded that for this group of patients the drug can be administered according to the same dose regimen as that used for normal subjects. Springer-Verlag, 1990 Lormetazepam nationallicence pharmacokinetics nationallicence bioavailability nationallicence cirrhotic patients nationallicence normal volunteers nationallicence Hildebrand M. Department of Pharmacokinetics, Schering AG, Berlin, FRG aut Hellstern A. Department of Internal Medicine, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG aut Hümpel M. Department of Pharmacokinetics, Schering AG, Berlin, FRG aut Hellenbrecht D. Department of Pharmacology and Toxicology, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG aut Saller R. Department of Internal Medicine, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG aut European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/1(1990-01-01), 19-26 0378-7966 15:1<19 1990 15 13318 https://doi.org/10.1007/BF03190123 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03190123 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hildebrand M. Department of Pharmacokinetics, Schering AG, Berlin, FRG aut NATIONALLICENCE 700 1- Hellstern A. Department of Internal Medicine, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG aut NATIONALLICENCE 700 1- Hümpel M. Department of Pharmacokinetics, Schering AG, Berlin, FRG aut NATIONALLICENCE 700 1- Hellenbrecht D. Department of Pharmacology and Toxicology, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG aut NATIONALLICENCE 700 1- Saller R. Department of Internal Medicine, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG aut NATIONALLICENCE 773 0- European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/1(1990-01-01), 19-26 0378-7966 15:1<19 1990 15 13318 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer