Repeated diazepam dosing in cirrhotic patients: cumulation and sedation

Clinical Pharmacology and Therapeutics
H R OchsR I Shader

Abstract

Five medically stable male patients with cirrhosis and four healthy age- and sex-matched controls received single 5-mg oral doses of diazepam (DZ) daily for 22 consecutive days. Plasma concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were measured daily during the period of dosing and in the 7-day washout period that followed. Clinical self-ratings of sedation, fatigue, mood state, and sleep patterns were obtained daily during the period of dosage with the use of visual analogue scales. Steady-state plasma DZ concentrations were higher (165 and 98 ng/ml), and DMDZ concentrations tended to be higher (399 and 206 ng/ml), in cirrhotics than in controls. Increases in self-rated daytime sedation also were greater in cirrhotics than in controls and correlated strongly with total DZ and DMDZ plasma concentration during the first 2 wk of diazepam dosing. Thus, reduced clearance of DZ in cirrhotics leads to increased cumulation during long-term dosing. This in turn is associated with increased clinical sedation. Sedative effects are partly offset as treatment proceeds because of adaptation or tolerance. Based on kinetic findings, diazepam can be given safely to cirrhotic patients provided daily dosage is reduced by...Continue Reading

Citations

Jan 1, 1986·European Journal of Clinical Pharmacology·H R OchsM Knüchel
Sep 17, 1987·The New England Journal of Medicine·D J GreenblattR I Shader
Feb 1, 1986·British Journal of Clinical Pharmacology·J M ScavoneR I Shader
Jan 1, 1984·European Journal of Clinical Pharmacology·H R OchsB Verburg-Ochs
Jun 1, 2005·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Fabiola DelcòStephan Krähenbühl
May 28, 2014·Current Treatment Options in Neurology·Nivedita U JerathMark Granner
Jan 1, 1985·Alcoholism, Clinical and Experimental Research·A Wilson, B A Vulcano
Aug 11, 1983·The New England Journal of Medicine·D J GreenblattD R Abernethy
Jun 21, 1984·The New England Journal of Medicine·D J GreenblattR I Shader
Jan 1, 1986·Acta Psychiatrica Scandinavica. Supplementum·D R AbernethyR I Shader
Jul 1, 1995·Clinical Pharmacology and Therapeutics·Y CaracoA J Wood
Aug 29, 2020·Journal of Clinical Pharmacology·David J GreenblattRichard I Shader
Oct 17, 2014·Journal of Clinical Psychopharmacology·David J Greenblatt
Feb 1, 1984·Journal of Clinical Pharmacology·R P JuhlR B Smith
May 4, 2007·Nature Clinical Practice. Gastroenterology & Hepatology·A James Hanje, Tushar Patel
Dec 11, 2020·Expert Review of Neurotherapeutics·Giovanni MastroianniEdoardo Ferlazzo
Jan 1, 1990·International Journal of Psychiatry in Medicine·R M Leipzig
Feb 16, 1988·European Journal of Pharmacology·K SzczawińskaA Chodera
Jun 18, 2010·Seizure : the Journal of the British Epilepsy Association·J Ruiz-GiménezUNKNOWN Andalusian Epilepsy Society

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