Add time:07/18/2019         Source:sciencedirect.com

This study was performed to determine delavirdine protein-binding characteristics as well as those of its N-dealkylated metabolite (N-DLV). Initial studies of 36 μM delavirdine and 30 μM N-DLV in solutions of plasma, albumin 4 g%, alpha-1-acid glycoprotein (AAG) 100 mg% or immune globulin (IVIG) 5 g% were conducted. Delavirdine (12, 36 and 73 μM) and N-DLV (10, 30 and 60 μM) were then studied alone and in combination in plasma and various concentrations of albumin. Studies were done in triplicate using equilibrium dialysis. The mean delavirdine fraction unbound (fu) in plasma, albumin, IVIG and AAG was 0.013, 0.033, 0.752 and 0.912 while the mean fu of N-DLV in these same protein solutions was 0.139, 0.195, 0.329 and 0.359. In plasma and albumin, a greater fu was observed at higher delavirdine concentrations and no significant changes in fu were noted with the addition of N-DLV. An increase in delavirdine fu was noted as the albumin concentrations decreased. The fu of N-DLV increased significantly as the concentration of albumin decreased as well as with decreasing N-DLV concentration. The potential implications of extensive delavirdine binding to plasma proteins, primarily albumin, are discussed.

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