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Effect of plasma protein and tissue binding on the biologic half‐life of drugs
Author(s) -
Gibaldi Milo,
Levy Gerhard,
McNamara Patrick J.
Publication year - 1978
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/cpt19782411
Subject(s) - pharmacokinetics , plasma protein binding , kinetics , blood proteins , plasma clearance , drug , chemistry , pharmacology , plasma concentration , perfusion , biotransformation , half life , plasma levels , medicine , biochemistry , enzyme , physics , quantum mechanics
It is now generally appreciated that there can be pronounced interindividual differences in plasma protein binding of many drugs because of genetic, 13 environmental (drug interaction), 11 and pathologic 7 factors and aging. 1 Pharmacokinetic theory has been developed to relate quantitatively the effect of changes in plasma protein binding to changes in the elimination kinetics of drugs. 8,14 In the case of drugs that are eliminated almost entirely by hepatic biotransformation with linear (apparently nonsaturable) kinetics not limited by organ perfusion rate, it has been shown that the total clearance (Cl) is directly proportional to the free fraction of drug in plasma (f p ), i.e.,