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Estimation of serum protein binding of compounds metabolized in serum using matrix inhibition
Author(s) -
Uchimura Takahide,
Kato Motohiro,
Shiokawa Rie,
Nabuchi Yoshiaki,
Saito Kimitoshi,
Kinoshita Haruki
Publication year - 2008
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.610
Subject(s) - ultrafiltration (renal) , chemistry , chromatography , matrix (chemical analysis) , incubation , plasma protein binding , phosphate buffered saline , free fraction , blood proteins , binding protein , biochemistry , gene
It is difficult to evaluate the serum protein binding of compounds that are metabolized in rat serum, even when using ultrafiltration. Protein binding was estimated using matrix inhibition, a method that uses the change in metabolic velocity achieved by changing the free fraction of a compound in the incubation mixture by diluting the serum with phosphate buffered saline. The T 1/2 of phenyl nicotinate, benzyl nicotinate, octyl nicotinate, hexyl nicotinate, butyl nicotinate and [ 3 H] compound A were 0.165, 0.780, 2.62, 3.94, 5.22 and 135 min, respectively, with protein binding values of 82.1%, 91.6%, 98.8%, 98.5%, 85.5% and 96.9%. The protein binding value of compound A estimated by ultrafiltration was 93.4%, indicating that the two methods give similar values. The matrix inhibition method is thus applicable for the evaluation of compounds metabolized in serum, and provides a simple, useful method to determine protein binding. Copyright © 2008 John Wiley & Sons, Ltd.