The pharmacokinetics of
butofilolol, a new beta-blocking
drug used in the treatment of
hypertension, were investigated in 9 patients with varying degrees of renal impairment (
creatinine clearance ranging from 65 ml/min to 6.6 ml/min). The
drug was administered as a single oral 100-mg dose. Plasma and urine concentrations of the parent
drug were measured. The pharmacokinetic parameters of
butofilolol calculated from examination of patients with
renal failure were compared to those obtained from healthy subjects.
Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent
drug whereas its elimination rate constant tended to increase, especially in severe
renal failure. A highly significant relationship between the amounts of unchanged
drug excreted in urine and the
creatinine clearance was observed (r = 0.90, p less than 0.001). The higher plasma levels of the parent
drug observed in
renal failure might be due to a decrease in the first-pass hepatic extraction of the
drug. But these changes in plasma clearance were probably counteracted by modification of the volume of distribution, so that the net result of these alterations was a slight increase in the elimination half-life.