Abstract
The binding of LHRH and [6-(3-(2-naphthyl)-D-Ala]LHRH (nafarelin acetate), a highly potent LHRH agonist, to plasma proteins was investigated in vitro by equilibrium dialysis at 4 degrees C with fresh plasma from normal human subjects, female rhesus monkeys, and female rats. Over a wide range of concentrations (10(-8) to 10(-5) M), 78-84% of nafarelin acetate and only 22-25% of LHRH were bound to undiluted plasma. With 10% plasma, the extent of binding was 31-37%, and 0.9-4.2% for nafarelin acetate and LHRH, respectively. Albumin was shown to play a predominant role in the plasma binding of the two compounds. The considerable differences in the extent of binding of nafarelin acetate and LHRH to plasma may contribute to some of the differences in pharmacokinetic parameters observed for the two compounds.
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