IN-VITRO PROTEIN-BINDING CHARACTERISTICS OF DELAVIRDINE AND ITS N-DEALKYLATED METABOLITE

This study was performed to determine delavirdine protein-binding char acteristics as well as those of its N-dealkylated metabolite (N-DLV). Initial studies of 36 mu M delavirdine and 30 mu M N-DLV in solutions of plasma, albumin 4 g%, alpha-1-acid glycoprotein (AAG) 100 mg% or im mune globulin (IVIG) 5 g% were conducted. Delavirdine (12, 36 and 73 m u M) and N-DLV (10, 30 and 60 mu M) were then studied alone and in com bination in plasma and various concentrations of albumin. Studies were done in triplicate using equilibrium dialysis. The mean delavirdine f raction unbound (f(u)) in plasma, albumin, IVIG and AAG was 0.013, 0.0 33, 0.752 and 0.912 while the mean f(u) of N-DLV in these same protein solutions was 0.139, 0.195, 0.329 and 0.359. In plasma and albumin, a greater f(u) was observed at higher delavirdine concentrations and no significant changes in f(u) were noted with the addition of N-DLV. An increase in delavirdine f(u) was noted as the albumin concentrations decreased. The f(u) of N-DLV increased significantly as the concentrat ion of albumin decreased as well as with decreasing N-DLV concentratio n. The potential implications of extensive delavirdine binding to plas ma proteins, primarily albumin, are discussed.