Pharmacokinetics and Hepatic Extraction Ratio of Pindolol in Hypertensive Patients with Normal and Impaired Renal Function

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Abstract
The i.v. and oral pharmacokinetics and the hepatic extraction ratio of pindolol were determined in 24 hypertensive patients with normal or impaired renal function. In patients with normal renal function the total clearance was the sum of equal parts of the renal and nonrenal clearances. The nonrenal clearance was equal to the hepatic clearance directly measured from the hepatic extraction ratio. Compared to patients with normal renal function, patients with chronic renal failure exhibited unchanged K12 [microscopic rate constants] and K21, and nonrenal clearances, and significantly decreased values in half-life of the .beta. [elimination rate constant] phase, Kel and total renal clearance. The renal clearance was positively correlated (P < 0.01) to the creatinine clearance. Bioavailability was significantly reduced (P < 0.01) in the patients with renal failure. Assuming that the nonrenal clearance was equal to the hepatic clearance, evidence indicates that, in patients with renal insufficiency no increased metabolism accompanies the decrease in renal function and decreased availability is due to reduced absorption.