The study of protein binding of anti-tuberculous drugs is of clinical interest, since the degree of tissue penetration and possibly frequency of adverse drug reactions may be expected to be related to free drug concentration and, hence, inversely related to the degree of protein binding. Variations in free drug concentration may result from changes in plasma protein concentration with age or disease. Albumin and α-l-acid glycoprotein are two major drug binding proteins (1,2). Age and disease have been shown to affect the concentration of both proteins (3,4). To date there is little data on protein binding of isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZ). Information is available for isoniazid and rifampicin binding to serum proteins, but not to individual drug-binding proteins. Little information is available regarding percentage binding with changes in protein concentrations. Such data would be particularly relevant in treatment of tuberculosis in the elderly, where there is an increased incidence of side effects (5). It is known that age, disease, or malnutrition result in lower serum albumin concentrations, while α-1-acid glycoprotein increases with age (2,6). Although no difference in total plasma anti-tuberculous drug concentrations has been observed between young and elderly patients (7), the difference in serum drug-binding protein concentration may give rise to differences in free drug concentration, possibly contributing to the differences in incidences of adverse drug reactions in the young and elderly. In this study, we examined the degree of binding of INH, RIF, and PZ to plasma, albumin, and α-1-acid glycoprotein, and the effect of variations in protein concentration on the degree of binding.
- In Vitro protein binding,
- Whole Plasma,
- ?-1-Acid Glycoprotein
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