EUROPEAN JOURNAL OF DRUG METABOLISM ANDPHARMACOKRfflTICS, 1990,Vol. IS, No. I, pp. 19-26

Plasma levels and urinary excretion of lormetazepam in patients with liver cirrhosis and in healthy volunteers M.lllLDEBRAND I , A. HELLSTERN2, M. HUMPEL I , D. HELLENBREC~ and R. SALLER2 1Department ofPharmacokinetics, Schering AG, Berlin, FRG 2Department of InternalMedicine, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG 3Department ofPharmacology and Toxicology, Johann Wolfgang von Goethe University, Frankfurt/Main, FRG

Received for publication: October 12, 1988

Keywords: Lormetazepam, pbannacokinetics, bioavailability, cirrhotic patients, normal volunteers

SUMMARY Plasma levels and urinary excretion of lormetazcpam (Noctamid~-ampoulcs; 2 mgI10 ml) were studied after i.v. (0.015 mglkg b.w.) and after p.o (0.03 mglkg b.w.) ~tration 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 nglml [C] vs. 11-16 nglml [N]) and highC2' AUCo-24 values of the unchanged drug (i.v.; 66-102 ng.hlml [CJ vs. 54-72 ng.hlml [NJ; p.o.: 83-188 ng.hlml [C] vs. 74-113 ng.hlml [NJ). The absolute bioavailability was increased in the C-group with 57-134% vs. 52-84% [NJ. The total plasma clearance of lormetazepam was 3 ml/minlkg in the C-group and 4 ml/minlkg in the N-group and thus within the range known for elderly and young male subjects. Conversely to the parent compound, the AUC-figurcs of its 3-0H-glucuronide were higher in the N-group (34