FAZADINIUM PHARMACOKINETICS IN PATIENTS WITH LIVER DISEASE

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Abstract
Serum concentrations of fazadinium were measured in eight patients with cirrhosis and eight patients with total binary obstruction who underwent abdominal surgery. A biexponential decay of the concentration was observed after a single i.v. injection of fazadinium. A two-compartment open model was used in the pharmacokinetic analysis of the data. The pharmacokinetic parameters were compared with those obtained in 11 normal patients. A 90% increase in both the distribution half-life (T½α), from 10 min to 19 min, and in the elimination half-life (T½β)3 from 82 min to 153 min, was observed in patients with cirrhosis. These changes are the consequence of an increase (60%) in the total apparent volume of distribution {V). In contrast, the plasma clearance (CI) was not modified. Total biliary obstruction was associated with very little change in the pharmacokinetics of fazadinium, T½β being slightly prolonged to 103 min. No significant decrease in plasma clearance was observed in patients with cholestasis. These results suggest that biliary excretion of fazadinuim does not represent an important supplementary pathway to renal excretion. The relatively rapid decrease of the blood concentration of fazadinium compared with other non-depolarizing relaxants is probably related to another extrarenal pathway of elimination which has not yet been identified.

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