PHARMACOKINETIC AND BLOOD-PRESSURE OF CARVEDILOL IN PATIENTS WITH CHRONIC-RENAL-FAILURE

The pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51-90 ml.min-1; II 26-50 ml.min-1; III 4-25 ml.min-1. The area under plasma level time curve AUC, the elimination half-life t1/2, the maximum plasma concentration C(max), the time to peak concentration t(max) were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine A(e) and the renal clearance CL(R) of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure.