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Disposition of propranolol VI. Independent variation in steady‐state circulating drug concentrations and half‐life as a result of plasma drug binding in man
Author(s) -
Evans Gwyn H,
Shand David G.
Publication year - 1973
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 - 10.1002/cpt1973144part1494
Subject(s) - volume of distribution , propranolol , pharmacokinetics , drug , half life , chemistry , free fraction , distribution (mathematics) , steady state (chemistry) , pharmacology , elimination rate constant , whole blood , drug metabolism , blood plasma , blood proteins , blood volume , endocrinology , medicine , biochemistry , mathematical analysis , mathematics
Plasma binding of propranolol has been measured at therapeutic concentrations in 6 subjects in whom steady‐state blood concentrations and half‐life had been measured during chronic oral administration of 80 mg every 6 hours. Neither steady‐state blood concentrations nor drug clearance (Cl ** ) was related to binding of drug in the blood. Volume of distribution (Vd β ), however, increased as the fraction of free drug in the blood (fb) increased, such that the volume of distribution of free drug (Vdp/fb) was relatively constant. Drug half‐life was proportional to fb/Cl ** since it was a function of both Vdp and clearance that varied independently. These data show that propranolol can be classified as a drug whose hepatic elimination is not restricted to the free drug in the circulation, so that binding to elements in the blood accelerates its elimination rate by acting as a carrier system from the tissues to its site of elimination and that this occurs without alteration drug clearance or steady‐state total blood concentrations.