Drug Research Unit, University of California, San Francisco, CA 94143-0622, USA.
HIV Med. 2010 Apr;11(4):232-8. doi: 10.1111/j.1468-1293.2009.00767.x. Epub 2009 Dec 3.
Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and alpha-1 acid glycoprotein (AAG). Small changes in PB can greatly impact the fraction of drug unbound (FU) exerting pharmacological effect. We report lopinavir (LPV) PB during third trimester (antepartum, AP) compared to > or =1.7 weeks postpartum (PP) to determine if FU changes compensate for reduced total concentrations reported previously.
P1026s enrolled women receiving LPV/ritonavir, soft gel capsules 400/100 mg or 533/133 mg twice daily. LPV FU, albumin and AAG were determined AP and PP.
AP/PP samples were available from 29/25 women respectively with all but one woman receiving the same dose AP/PP. LPV FU was increased 18% AP vs. PP (mean 0.96+/-0.16% AP vs. 0.82+/-0.21% PP, P=0.001). Mean protein concentrations were reduced AP (AAG=477 mg/L; albumin=3.28 mg/dL) vs. PP (AAG=1007 mg/L; albumin=3.85 mg/dL) (P<0.0001 for each comparison). AAG concentration correlated with LPV binding. Total LPV concentration did not correlate with LPV FU AP or PP. However, higher LPV concentration PP was associated with reduced PB and higher FU after adjustment for AAG.
LPV FU was higher and AAG lower AP vs. PP. The 18% increase in LPV FU AP is smaller than the reduction in total LPV concentration reported previously and is not of sufficient magnitude to eliminate the need for an increased dose during pregnancy.
由于白蛋白和α-1酸性糖蛋白（AAG）的血浆浓度变化，妊娠可能会改变高度结合的蛋白酶抑制剂的蛋白结合（PB）。PB 的微小变化会极大地影响发挥药理作用的未结合药物分数（FU）。我们报告了第三孕期（产前，AP）洛匹那韦（LPV）的 PB 与 > 或 =1.7 周产后（PP）相比，以确定 FU 的变化是否可以弥补先前报道的总浓度降低。
P1026s 纳入了每天接受 LPV/ritonavir 软胶囊 400/100mg 或 533/133mg 两次的妇女。AP 和 PP 时测定 LPV FU、白蛋白和 AAG。
分别有 29/25 名妇女的 AP/PP 样本可用，除一名妇女外，所有妇女在 AP/PP 时均接受相同剂量。AP 与 PP 相比，LPV FU 增加了 18%（平均 0.96+/-0.16%AP 与 0.82+/-0.21%PP，P=0.001）。AP 的平均蛋白浓度降低（AAG=477mg/L；白蛋白=3.28mg/dL）与 PP（AAG=1007mg/L；白蛋白=3.85mg/dL）（每种比较均 P<0.0001）。AAG 浓度与 LPV 结合相关。AP 或 PP 时，总 LPV 浓度与 LPV FU 不相关。然而，在调整 AAG 后，PP 时较高的 LPV 浓度与降低的 PB 和较高的 FU 相关。
AP 与 PP 相比，LPV FU 较高，AAG 较低。AP 时 LPV FU 增加 18%，小于先前报道的总 LPV 浓度降低，并且不足以消除妊娠期间增加剂量的需要。
