Bilello J A, Bilello P A, Prichard M, Robins T, Drusano G L
Department of Medicine, Albany Medical College, New York 12208.
J Infect Dis. 1995 Mar;171(3):546-51. doi: 10.1093/infdis/171.3.546.
Since plasma protein binding of antiinfectives can adversely affect drug activity, the effect of serum proteins on the in vitro antiviral activity of A77003, a human immunodeficiency virus type 1 (HIV) protease inhibitor, was investigated. In vitro, A77003 is effective in both acute and chronic infection in 10% fetal bovine or human serum. As the concentration of human serum was increased to 50%, antiviral efficacy decreased 3- to 6-fold. Purified human alpha 1 acid glycoprotein (alpha 1-AGP) at physiologic concentrations (0.5-2 mg/mL) dose-dependently reduced the antiviral activity of A77003. alpha 1-AGP at 1 mg/mL also antagonized the anti-HIV activity of A77003-zidovudine combinations. Therefore, higher concentrations of HIV protease inhibitors than would be predicted, on the basis of in vitro activity in the absence of physiologic concentrations of binding protein, may be required to effectively limit viral replication in vivo.
由于抗感染药物与血浆蛋白的结合可能会对药物活性产生不利影响，因此研究了血清蛋白对人免疫缺陷病毒1型（HIV）蛋白酶抑制剂A77003体外抗病毒活性的影响。在体外，A77003在10%胎牛血清或人血清中对急性和慢性感染均有效。当人血清浓度增加到50%时，抗病毒效力降低了3至6倍。生理浓度（0.5 - 2mg/mL）的纯化人α1酸性糖蛋白（α1-AGP）剂量依赖性地降低了A77003的抗病毒活性。1mg/mL的α1-AGP也拮抗了A77003与齐多夫定联合用药的抗HIV活性。因此，在体内有效限制病毒复制可能需要比根据在不存在生理浓度结合蛋白时的体外活性所预测的更高浓度的HIV蛋白酶抑制剂。
