Table 1.
Fatty Acid | Change in Free Drug Concentrationa | ||
---|---|---|---|
Acetohexamide | Gliclazide | Tolbutamide | |
Lauric acid (0.1–6 μM) | |||
Normal HSA | 0.2–10% | 0.03–2.1%b | 0.04–2.7% |
Glycated HSA | 0.04–2.6%b,c | 0.1–7% | 0.02–1.0%b,c |
Linoleic acid (20–93 μM) | |||
Normal HSA | 3.2–15% | 5–24% | 2.4–11% |
Glycated HSA | 6–29%c | 5–23%c | 8–38% |
Myristic acid (3–24 μM) | |||
Normal HSA | 2.6–20% | 0.6–4.6%b | 0.04–0.3%b |
Glycated HSA | 1.0–8%c | 0.3–2.5%c | 0.5–4.2%c |
Oleic acid (33–182 μM) | |||
Normal HSA | 17–93% | −1.5–8%a | 9–35%d |
Glycated HSA | 0.4–2.1% | 9–21%b | 1.5–8% |
Palmitic acid (25–171 μM) | |||
Normal HSA | 4.0–27%d | 4.3–29% | 4.3–29% |
Glycated HSA | 1.5–10%c | 1.3–9% | 5–36%c |
Stearic acid (6–57 μM) | |||
Normal HSA | 0.6–5% | 4.4–41% | 19–31%d |
Glycated HSA | 0.6–5%c | 1.5–14% | 2.8–25%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; the given values represent 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 normal 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.
Non-linear regression or a combination of linear regions were used in this case because some curvature was noted in the corresponding plot of free drug concentration versus fatty acid concentration.