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Protein binding can impair the potency of human immunodeficiency virus (HIV) protease inhibitors. Therefore, the activity of a novel compound, CGP 61755, was studied in the absence or presence of alpha1-acid glycoprotein (alpha1AGP). In MT-2 cells, the activity loss was 4-fold (EC90 without alpha1AGP, 29 nM vs. 122 nM with alpha1AGP). In primary lymphocytes, the loss was 8-fold (EC90, 45 nM vs. 364 nM). In identical experiments, the activity loss in MT-2 cells and lymphocytes was 2- and 3-fold, respectively, for indinavir, 11- and 10-fold for saquinavir, and 11- and 48-fold for ritonavir. For SC-52151, a 17-fold loss was seen in MT-2 cells, whereas no EC90 with alpha1AGP was reached in lymphocytes. This study demonstrates that the impact of alpha1AGP on in vitro activity varies greatly among different HIV protease inhibitors. The magnitude of such differences is greater in human lymphocytes than in a standard cell line.

the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases

In Vitro Effect of α<sub>1</sub>‐Acid Glycoprotein on the Anti‐Human Immunodeficiency Virus (HIV) Activity of the Protease Inhibitor CGP 61755: A Comparative Study with Other Relevant HIV Protease Inhibitors

In Vitro Effect of α1‐Acid Glycoprotein on the Anti‐Human Immunodeficiency Virus (HIV) Activity of the Protease Inhibitor CGP 61755: A Comparative Study with Other Relevant HIV Protease Inhibitors

In Vitro Effect of α₁‐Acid Glycoprotein on the Anti‐Human Immunodeficiency Virus (HIV) Activity of the Protease Inhibitor CGP 61755: A Comparative Study with Other Relevant HIV Protease Inhibitors