Pharmacokinetic and pharmacodynamic modelling of atenolol in rabbits maintained on continuous peritoneal dialysis.

Abstract

The pharmacokinetic and pharmacodynamic profiles of atenolol were studied in adult male rabbits on continuous peritoneal dialysis given 3 mg/kg i.v. before and during renal failure. The average terminal elimination half-life for the drug was 2.5 h calculated from blood, dialysate or urinary data. This value increased about nine times in anuric conditions. Although atenolol was eliminated in the peritoneal fluid, the amount excreted was relatively low both in normal conditions and renal failure, respectively 0.6 and 7% of the administered dose. The pharmacokinetic model was extended by an "effect compartment", which has no influence on the predetermined mass of drug in the body, to analyse the relationship between heart rate fall and changes in atenolol blood concentrations. After drug administration, heart rate fell rapidly about 90 beats in both states. The mean equilibration half-time of atenolol effect and blood concentrations was 0.7 and 1.5 h in normal and pathological states, respectively. The mean blood concentration required to produce 50% of heart rate fall was similar in both conditions, 0.23 mg/l. The nine-fold decrease of atenolol elimination in anuria was in good agreement with the increase in duration of the drug's effect, and was suitably described by the "effect model".