ABSTRACT
The effect of cirrhosis on the pharmacokinetics and plasma protein binding of thiopental was studied in eight patients with cirrhosis, aged (mean +/- SD) 42 +/- 11 yr, and nine patients with normal hepatic and renal function, aged 48 +/- 12 yr, undergoing elective abdominal or orthopedic surgery. The total apparent volume of distribution at steady state was of 2.3 +/- 0.5 1 X kg-1 in the controls and of 3.5 +/- 1.9 1 X kg-1 in the patients with cirrhosis. Thiopental plasma clearance based upon total drug concentrations was 3.9 +/- 1.2 ml X min-1 X kg-1 in the normal group and did not differ significantly in the patients with cirrhosis: 4.4 +/- 2.2 ml X min-1 X kg-1. The elimination half-life was of 529 +/- 97 min in the controls and of 714 +/- 252 min in the patients with cirrhosis. The thiopental free fraction was 14.5 +/- 3.4% in the controls and was increased significantly to 25.2 +/- 3.9% in the patients with cirrhosis. Thiopental intrinsic clearance was decreased insignificantly (P = 0.06) from 28.3 +/- 9.0 ml X min-1 X kg-1 in the controls to 18.2 +/- 10.5 ml X min-1 X kg-1 in those with cirrhosis, suggesting that these patients may have a decreased capacity for thiopental metabolism. These results suggest that the risk of a prolonged effect following thiopental administration appears unlikely in patients with cirrhosis.
Subject(s)
Liver Cirrhosis/metabolism , Thiopental/metabolism , Adult , Aged , Blood Proteins/metabolism , Female , Half-Life , Humans , Kinetics , Liver Cirrhosis, Alcoholic/metabolism , Male , Metabolic Clearance Rate , Middle Aged , Protein Binding , Thiopental/bloodABSTRACT
It is reported the first observation of cardiogenic shock without delay, in a leukemic patient during a first injection of Rubidazone (22050 RP) which is recognized so far, as one of the least cardiotoxic anthracyclines. It has been concluded: --anthracyclines, beside the risk of a progressive cardiomyopathy which is related to the dose and very well known, can induce immediate cardiac injuries, which cannot be predicted yet; --the perfect myocardial protector is still to be discovered; --in this case, beta-adrenergic stimulators appeared to be able to control the cardiotoxic effect of Rubidazone; --the last fact could be considered in the decision to maintain the treatment when such an injury occurs during a chemotherapy or when it seems absolutely necessary to use such a drug.
