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Serum Binding of Indapamide in Health and Disease: Primary Role of α1‐acid glycoprotein
Author(s) -
Urien Saik,
Morin Didier,
d'Athis Philippe,
Coulomb Bertrand,
Tillement JeanPaul
Publication year - 1988
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 - 10.1002/j.1552-4604.1988.tb05760.x
Subject(s) - indapamide , orosomucoid , nefa , medicine , endocrinology , free fraction , albumin , serum albumin , human serum albumin , glycoprotein , chemistry , pharmacokinetics , biochemistry , blood pressure , insulin
The serum concentrations of alpha‐1‐acid glycoprotein (AAG), albumin (HSA), and nonesterified fatty acids (NEFA), and the serum binding of indapamide were measured in four groups of individuals: control (healthy) subjects (N = 24), patients with inflammatory syndrome (N = 28), with hepatic (N = 20) and renal (N = 27) insufficiency. Indapamide serum binding was increased in patients with inflammatory syndrome (82.2 ± 3.4%, P < .001), decreased in patients with hepatic insufficiency (72.3 ± 5.9%, P < .001) and unchanged in patients with renal insufficiency (77.7 ± 2.8%) as compared with controls (78.2 ± 3.1%). A multivariate analysis indicated that these changes were mainly related to concomitant changes in AAG concentration (that explained 63% of intersubject variability in bound/free binding ratio), and to a lesser extent to HSA (that explained only 4% of the variability in the binding). These data show that the free fraction of the acidic drug indapamide in serum is affected by pathologic conditions in which changes in AAG concentration occur and that, unexpectedly, HSA plays a negligible role in the binding.