Butofilolol

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.

The pharmacokinetics of butofilolol, a new beta-blocking drug, was studied in 6 healthy subjects. Plasma concentrations and urinary excretion of the unchanged drug were determined after a single 100-mg oral administration, and also during chronic treatment (100 mg/day for a week) and after the last dose. Maximum plasma concentrations were observed 2 to 3 h after drug administration and varied between the subjects (120 to 430 ng/ml). The apparent volumes of distribution were large, ranging between 200 I and 500 I, and the apparent clearances of elimination appeared to be intermediate between 40 and 70 l/h. Drug elimination in the urine (about 4% of administered dose) occurred by filtration, tubular secretion and pH-sensitive reabsorption following a non-linear process. However, pharmacokinetic parameters remained constant during chronic treatment, since urinary elimination of the parent drug was too low to influence its pharmacokinetic profile. In addition, a high correlation was found between plasma levels of butofilolol and the effect of the drug on resting heart rate, while a slight effect on diastolic blood pressure could be discerned.