Variation in serum binding of tertatolol mediated by disease-induced modification of alpha-acid glycoprotein concentration
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The serum concentrations of α1-acid glycoprotein (AAG), albumin (HSA) and non-esterified fatty acids, and the serum binding of tertatolol were measured in four groups of individuals: healthy control subjects (n=24), and patients with inflammation (n=28), and hepatic (n=20) and renal (n=27) insufficiency.
Serum binding of tertatolol was increased in patients with inflammation (94.6%), decreased in patients with hepatic insufficiency (88.8%) and it was unchanged in patients with renal insufficiency (92.8%) as compared to controls (92.7%).
Multivariate analysis indicated that the changes were mainly related to concomitant changes in AAG concentration, which could account for 57% of intersubject variability in the bound/free ratio, and to a lesser extent in HSA, which accounted for only 4% of the variability in the binding.
The data show that the free fraction of the basic drug tertatolol in serum is affected by pathological conditions that cause changes in AAG concentration.
Key wordstertatolol alpha1-acid glycoprotein serum binding AAG-drug interaction renal failure hepatic failure inflammatory syndromes
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