Pharmacokinetics of benzodiazepine antagonist Ro 15-1788 in cirrhotic patients with moderate or severe liver dysfunction

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
G Pomier-LayrarguesR F Butterworth

Abstract

Ro 15-1788, a benzodiazepine antagonist, has been advocated as a new treatment for hepatic encephalopathy. This drug is extensively metabolized by the liver in normal subjects. In the present study, we examined Ro 15-1788 disposition in eight healthy controls (Group I), eight cirrhotic patients with moderately impaired liver function (Pugh score less than 10, Group II) and eight patients with severe liver dysfunction (Pugh score greater than 10, Group III). The subjects of each group were age and sex matched. After an intravenous infusion of 2 mg Ro 15-1788 over 5 min, blood samples were taken at fixed intervals up to 7 hr after the infusion. Plasma levels of the drug were determined by capillary gas chromatography. In controls, Ro 15-1788 had a high plasma clearance [16.3 +/- 2.6 ml per min per kg (mean +/- S.D.)], a short half-life (45.7 +/- 8.5 min), a large volume of distribution (0.62 +/- 0.09 liter per kg) and a low plasma protein binding (45 +/- 6%). Plasma clearance was reduced markedly in both groups of cirrhotic patients (-57 and -74%, respectively); the volume of distribution was unchanged in Group II and moderately increased in Group III (+37%). The elimination half-life was markedly prolonged in Groups II and III (...Continue Reading

References

Jul 1, 1987·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J E MaddisonG C Farrell

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Citations

Aug 8, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G BarbaroG Barbarini
Jan 1, 1992·European Journal of Clinical Pharmacology·G M Robertz-VaupelH J Dengler
May 26, 2005·Neurochemistry International·Samir AhbouchaRoger F Butterworth
Apr 21, 2005·Journal of Neurosurgical Anesthesiology·Masayuki YanoTatsuru Arai
Jan 1, 1990·Acta Anaesthesiologica Scandinavica. Supplementum·R Amrein, W Hetzel
Jan 1, 1991·European Journal of Clinical Pharmacology·C C van der RijtM Schramel
Jan 1, 1991·Intensive Care Medicine·R Amrein, W Hetzel
Jan 1, 1994·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G Pomier-LayrarguesR F Butterworth
Mar 1, 1990·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R F Butterworth, G Pomier Layrargues
Dec 31, 2005·Metabolic Brain Disease·Samir Ahboucha, Roger F Butterworth

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