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Constant kinetics and constant concentration‐effect relationship during long‐term β3‐blockade with pindolol
Author(s) -
Galeazzi Renato L,
Pirovino Mauro,
Weidmann Peter
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.100
Subject(s) - pindolol , plasma renin activity , tachyphylaxis , endocrinology , medicine , chemistry , blockade , epinephrine , dose–response relationship , beta (programming language) , propranolol , receptor , renin–angiotensin system , blood pressure , computer science , programming language
Long‐term β‐blockade is said to increase the number of β‐receptors. The effect of β‐blockers could therefore be reduced after long use. We tested this hypothesis in nine healthy subjects given 15 mg pindolol daily for 4 wk. Plasma concentrations (measured fluorometrically), isoproterenol dose‐response relationship (to calculate the dose needed to increase heart rate by 25 bpm), renin, epinephrine, and norepinephrine were measured several times before and after the first and last dose. Kinetic parameters remained stable: total clearance (Cl tot ) = 45.2 and 42.9 l/hr, and Vd ss = 205.8 and 198.6 l after the first and last dose. The concentration‐effect relationship, plotted as the “dose ratio minus one” against the log of the plasma concentration was identical after 4 wk. Basal plasma renin activity was reduced slightly and the increase of stimulated plasma renin was blunted by pindolol even after 4 wk. The initial lowering of unstimulated renin by pindolol in the first 2 hr after dosing was not detectable after 4 wk. Epinephrine and norepinephrine levels in plasma were not changed initially nor after 4 wk. It is concluded that pindolol has a stable kinetic profile over time and that its β‐blockade does not induce tachyphylaxis. Clinical Pharmacology and Therapeutics (1983) 33 , 733–740; doi: 10.1038/clpt.1983.100