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In vitro studies on the blood distribution of almitrine.

Blood binding of almitrine, a highly lipophilic drug, was investigated in vitro. [3H]-Almitrine was incubated in a serum pool and isolated protein and lipoprotein fractions. The investigations were performed by using ultracentrifugation and another method which measures the uptake by proteins from glass beads coated with almitrine. Our results with ultracentrifugation show that the distribution of almitrine in serum takes place predominantly in the lipoprotein fraction (78%) and to a minor extent (22%) in the fraction of d greater than 1.20 (albumin-rich fraction). Experiments using glass beads coated with almitrine were then conducted to measure the binding of almitrine to isolated plasma proteins. The maximal uptake values (mol almitrine/mol lipoprotein) of almitrine by isolated lipoproteins decrease from VLDL (260) to LDL (20) to HDL (3) and seem to be related to the lipid content of the particles. The uptake by albumin and alpha 1-acid glycoprotein was low. The molar ratios of [almitrine]/[lipoprotein] are roughly proportional to almitrine concentrations within the therapeutic range. When almitrine was incubated in erythrocytes suspended in several dilutions of serum, almitrine partitioned less in erythrocytes as the serum protein concentration increased in the suspension.