The pharmacokinetics of
penbutolol, its 4-hydroxylated metabolite and of their conjugates was studied in hypertensive patients with various degrees of renal impairment. A single oral dose of
penbutolol 40 mg, was rapidly absorbed after a lag-time of 0.34 h. Its plasma concentration reached a maximum after 0.84 h and then declined bi-exponentially, with an apparent elimination half-life of 21.8 h. The hydroxylation of
penbutolol was negligible and conjugation was of major importance for its elimination. Consequently, the kinetics of unchanged
penbutolol were not altered by renal impairment. The 48 h-urinary excretion of
penbutolol and its metabolites reached 13-14% of the administered dose, which is consistent with extensive metabolism of the
drug.
After treatment for 30 days with
penbutolol 40 mg/d there was no accumulation of the parent
drug but the concentration of its conjugates was increased. It is concluded that the dose of
penbutolol need not be changed in patients with mild
renal insufficiency,
4-hydroxypenbutolol is unlikely to participate in the
anti-hypertensive effect of the
drug, due to its low concentrations, and biotransformation of
penbutolol may be enhanced during chronic treatment.