The efficacy of certain anti-tuberculosis drugs is affected by binding to alpha-1-acid glycoprotein.

Johnson, D A; Smith, Kevin

Abstract

One of the most ubiquitous plasma proteins, -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 -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 -1-acid glycoprotein levels increased during the acute phase response but specific -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.

Citation

Johnson, D. A., & Smith, K. (2006). The efficacy of certain anti-tuberculosis drugs is affected by binding to alpha-1-acid glycoprotein. Biomedical Chromatography, 20, 551-560. https://doi.org/10.1002/bmc.641

• Journal Article Type: Article
• Publication Date: Jun 15, 2006
• Deposit Date: Jun 27, 2008
• Print ISSN: 0269-3879
• Electronic ISSN: 1099-0801
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Pages: 551-560
• DOI: https://doi.org/10.1002/bmc.641
• Keywords: Alpha-1-acid glycoprotein; Tuberculosis medicines; Binding studies
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/1675
• Publisher URL: http://dx.doi.org/10.1002/bmc.641