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Evaluation of Highly Bound Drugs: Interspecies, Intersubject, and Related Comparisons
Author(s) -
Collins Jerry M.,
Klecker Raymond W.
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127000204200903
Subject(s) - dapsone , drug , human plasma , plasma protein binding , plasma concentration , chemistry , pharmacology , blood proteins , pharmacokinetics , dialysis , plasma , drug metabolism , chromatography , medicine , immunology , biochemistry , physics , quantum mechanics
Free (unbound) drug is generally the pharmacologically relevant param eter for drug exposure. Thus, comparisons among species, among individuals, and in other situations such as cell culture or drug metabolism experiments in vitro should be based on free drug. Although the traditional focus has been on the absolute value for free drug, the applications for the data in this study are primarily comparative. Therefore, the authors evaluated direct dialysis of one plasma sample versus another. At equilibrium, the total concentration of valproate in human plasma was 3‐fold higher than in rat plasma. The total concentration of monoacetyl dapsone was 10‐fold higher in human plasma than in rat plasma and 18‐fold higher in human plasma than in dog plasma. These results confirm predictions derived from conventional dialysis of each plasma sample separately versus buffer. These data can be interpreted directly, without interspecies correction factors for binding, especially for the most important cases—drugs that are highly protein‐bound.