We have compared in two separate studies the kinetics of ceftriaxone and cefotaxime in 8 cirrhotic patients with ascites and 8 control subjects after a single 20 min intravenous infusion of 1 g of each drug. The apparent volumes of distribution (Vz) were found to be significantly higher in cirrhotics than in control subjects (0.87, versus 0.49, l.kg-1, for cefotaxime and 0.23 versus 0.13 for ceftriaxone). The elimination kinetics of ceftriaxone were similar in the two groups. In contrast, the total and non-renal clearances of cefotaxime were reduced in cirrhotic patients. The two drugs rapidly entered the ascitic fluid. Peritoneal concentrations of ceftriaxone were higher than 7 micrograms.ml-1 from the second hour after the infusion and were 8.9 micrograms.ml-1 at 24 h. Peritoneal concentrations of cefotaxime were higher than 4 micrograms.ml-1 from 0.5 to 8 h after the infusion.
In the APOMYGRE trial, therapeutic MPA monitoring using a limited sampling strategy reduced the risk of treatment failure and acute rejection in renal allograft recipients during the first 12 months posttransplantation, at neutral cost.
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