Table 2.
Effects of elevated concentrations of fatty acids on the binding of sulfonylurea drugs to HSA and glycated HSA
| Fatty Acid | Change in Free Drug Concentrationa | ||
|---|---|---|---|
| Acetohexamide | Gliclazide | Tolbutamide | |
| Lauric acid (up to 9 μM) | |||
| Normal HSA | 13% | 3.1% | 3.9% |
| Glycated HSA | 3.8%b | 10% | 1.5%b,c |
| Linoleic acid (up to 300 μM) | |||
| Normal HSA | 49% | 76% | 36% |
| Glycated HSA | 94% | 76%c | 120% |
| Myristic acid (up to 43 μM) | |||
| Normal HSA | 37% | 8% | 0.6%b |
| Glycated HSA | 15% | 4.5%c | 8%c |
| Oleic acid (up to 600 μM) | |||
| Normal HSA | 310% | −27%a | 53% |
| Glycated HSA | 7% | 36% | 27% |
| Palmitic acid (up to 400 μM) | |||
| Normal HSA | 64% | 68% | 69% |
| Glycated HSA | 23% | 21% | 85% |
| Stearic acid (up to 80 μM) | |||
| Normal HSA | 8% | 57% | 37% |
| Glycated HSA | 7%c | 20% | 36%c |
All of the indicated changes are relative to the free concentration measured for a drug in the absence of any fatty acid at pH 7.4 and 37°C. Each of the given values represents an increase in the free drug concentration, except for the case of gliclazide in the presence of oleic acid and normal HSA.
All changes in the free drug concentration, except those indicated by this footnote, were significantly different at the 95% confidence level when comparing the results measured at the upper end of the elevated fatty acid concentration range versus the results obtained when no fatty acid was present.
All changes in the free drug concentration, except those indicated by this footnote, were significantly different at the 95% confidence level when comparing the results measured at the upper end of the normal fatty acid concentration range for normal HSA versus glycated HSA.