The binding of progabide and its metabolite, SL 75102, was studied in vitro by equilibrium dialysis. The progabide binding percentage in serum remained constant (approximately equal to 96%) over a wide range of concentrations. Binding of progabide was characterized by one class of sites to human serum albumin (HSA) (n = 3.8 +/- 0.2; K = 2.5 X 10(4) M-1). The binding to alpha 1 acid glycoprotein (AAG) was also shown to be saturable with n = 1.7 +/- 0.2 and K = 3.1 X 10(4) M-1. Progabide was bound to a lesser extent to red blood cells (RBC), lipoproteins and gamma-globulins. The SL 75102 binding percentage in serum remained constant (approximately equal to 98%), over a range of concentrations exceeding therapeutic levels. SL 75102 showed two saturable classes of binding sites to HSA: the first one with n1 = 0.8 +/- 0.1 and K1 = 10(6) M-1 and the second one with n2 = 7.9 +/- 0.2 and K2 = 8.1 X 10(3) M-1. The binding to AAG was also shown to be saturable with n = 0.7 +/- 0.1 and K = 1.6 X 10(4) M-1. SL 75102 was bound to a lesser extent to RBC, lipoproteins and gamma-globulins. The binding parameters were used to calculate the distribution of progabide and SL 75102 among the components in whole blood over the therapeutic range. The calculations showed that serum albumin was the major binding component for the parent drug and its metabolite.