Premium
The efficacy of certain anti‐tuberculosis drugs is affected by binding to α ‐1‐acid glycoprotein
Author(s) -
Johnson DeborahAnn,
Smith Kevin D.
Publication year - 2006
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.641
Subject(s) - chemistry , capreomycin , glycoprotein , glycosylation , rifampicin , orosomucoid , plasma protein binding , mycobacterium tuberculosis , aminosalicylic acid , isoniazid , pharmacology , bedaquiline , pyrazinamide , ethionamide , drug , biochemistry , blood proteins , free fraction , in vivo , tuberculosis , antibiotics , medicine , ethambutol , microbiology and biotechnology , pathology , biology
One of the most ubiquitous plasma proteins, α ‐1‐acid glycoprotein (AGP), has a high affinity, low capacity binding for basic drugs positively charged at physiological pH. Moreover, as an acute phase protein its level is increased in various disease states in a manner that is likely to influence the free plasma level of a drug, the ability to attain minimum effective concentration and overall in vivo effectiveness. AGP is a glycoprotein known to display disease specific changes in glycosylation and although this secondary modification is not directly involved in drug binding, it may influence the conformation of the binding site. Binding studies reveal that α ‐1‐acid glycoprotein bind mainly to the tuberculosis drugs: rifampicin; isoniazid; pyrazinamide; p‐aminosalicylic acid; capreomycin; ethionamide; levofloxacin and ofloxacin out with the therapeutic plasma range tested. These results are however still considered significant as not only are α ‐1‐acid glycoprotein levels increased during the acute phase response but specific α ‐1‐acid glycoprotein from tuberculosis samples are subject to glycosylation changes which can increase the binding affinity and cause binding to occur at the therapeutic concentration. Copyright © 2006 John Wiley & Sons, Ltd.