Colombo R, Pinelli A
Pharmacology. 1982;25(2):73-81. doi: 10.1159/000137726.
The in vivo effects of increased free fatty acid (FFA) plasma levels on the protein binding of furosemide were investigated in 30 adult-onset diabetics and 22 patients suffering from bacterial infections (gram- negative bacilli and gram-positive cocci). In diabetics, FFA were 2.43 +/- 1.63 mEq/l, and in subjects with bacterial infections 1.82 +/- 0.92 mEq/l. Furthermore, the percent of oleic acid and, to a very lesser extent, palmitoleic acid increased linearly with the increase of the FFA plasma level. The free furosemide fraction was about 1% or less in subjects with a molar ratio of FFA to albumin below 4, but a displacement of the drug from the plasma proteins occurred consistently when this ratio was above 4. At a molar ratio of FFA to albumin as high as 9.34, the free furosemide was 6.7% of the total concentration (8.9 microgram/ml). These results do not quantitatively agree with previous in vitro studies employing single fatty acids and human serum albumin, suggesting that in vivo plasma composition is not adequately reproduced during in vitro experiments on protein-binding displacement of drugs by FFA.
在30名成年发病型糖尿病患者和22名患有细菌感染（革兰氏阴性杆菌和革兰氏阳性球菌）的患者中，研究了血浆游离脂肪酸（FFA）水平升高对呋塞米蛋白结合的体内影响。糖尿病患者的FFA为2.43±1.63 mEq/l，细菌感染患者的FFA为1.82±0.92 mEq/l。此外，油酸百分比以及在非常小的程度上棕榈油酸百分比随血浆FFA水平的升高呈线性增加。在FFA与白蛋白摩尔比低于4的受试者中，游离呋塞米分数约为1%或更低，但当该比例高于4时，药物会持续从血浆蛋白中置换出来。在FFA与白蛋白摩尔比高达9.34时，游离呋塞米占总浓度（8.9微克/毫升）的6.7%。这些结果在数量上与先前使用单一脂肪酸和人血清白蛋白的体外研究不一致，表明在体外进行FFA对药物蛋白结合置换的实验期间，体内血浆成分未得到充分再现。
