PMID: 2096104Jan 1, 1990Paper

Pharmacokinetics of flunitrazepam following single dose oral administration in liver disease patients compared with healthy volunteers

Fundamental & Clinical Pharmacology
C Drouet-CoassoloJ P Cano

Abstract

The pharmacokinetic behaviour of flunitrazepam and its main active metabolite, N-desmethyl flunitrazepam, was investigated in 12 patients with liver disease (cirrhosis or hepatitis) compared to 6 healthy volunteers. A gas-liquid chromatographic method allowing for simultaneous determination of flunitrazepam and N-desmethyl flunitrazepam in plasma samples was developed. The accuracy and the precision near the quantification limit of ca. 1 ng/ml were better than 5%. Plasma levels of flunitrazepam were not significantly altered by hepatic failure, whereas plasma levels of N-desmethyl flunitrazepam were lower in patients than in healthy subjects. Pharmacokinetic parameters did not differ significantly between healthy subjects and liver disease patients: the oral clearance was 3.5 +/- 0.8, 3.5 +/- 1.9 and 4.0 +/- 1.2 ml/min/kg, respectively in healthy subjects, patients with hepatitis and patients with cirrhosis. The apparent elimination half-life was 22 +/- 5 h in healthy subjects, 25 +/- 10 h in patients with hepatitis and 20 +/- 6 h in patients with cirrhosis. However, the expected increase of the drug free fraction during liver disease could decrease the therapeutic and toxic ranges of flunitrazepam in these patients.

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Citations

Aug 16, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Stéphane PirnayFrédéric J Baud
Jun 18, 2009·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Chantal SchlatterStephan Krähenbühl
Sep 30, 2005·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H C RawdenJ B Houston
Oct 5, 2018·European Journal of Drug Metabolism and Pharmacokinetics·Zorica JovićMarina Kostić
Jan 18, 2006·Digestive Diseases and Sciences·Yasser M BhatThomas A Shaw-Stiffel
Jun 1, 1991·Alcoholism, Clinical and Experimental Research·J Johnsen, J Mørland
Nov 1, 1995·Special Care in Dentistry : Official Publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry·C S SolomonT M Arendorf
Sep 14, 2015·European Journal of Clinical Pharmacology·Mary MorrisonChristophe Schmitt
Mar 18, 2003·Journal of Clinical Psychopharmacology·I GafniE M Sellers
Jan 28, 2017·Forensic Toxicology·Maria KatselouSotiris Athanaselis
Apr 3, 2018·Molecular Pharmaceutics·Jaydeep YadavSwati Nagar

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