Gleisner, F. Ibrahim and L. Campbell); Mortimer Market Centre, London (R. Gilson, N. Brima and I. Williams); North Middlesex University Hospital NHS Trust, London (A. Schwenk, J. Ainsworth, C. Wood and S. Miller); Royal Free NHS Trust and UCL Medical ITF2357 ic50 School, London (M. Johnson, M. Youle, F. Lampe, C. Smith, H. Grabowska, C. Chaloner and D. Puradiredja); St Mary’s Hospital, London (J. Walsh, J. Weber, F. Ramzan, N. Mackie and A. Winston); The Lothian University Hospitals NHS Trust, Edinburgh
(C. Leen and A. Wilson); North Bristol NHS Trust (M. Gompels and S. Allan); University of Leicester NHS Trust (A. Palfreeman and A. Moore); South Tees Hospitals NHS Foundation Trust (D. Chadwick and K. Wakeman). “
“Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and α-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 ≥1.7 weeks postpartum (PP) to determine Tanespimycin 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) Liothyronine Sodium (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. The current US Public Health Service (USPHS) Perinatal Guidelines recommend treatment with highly active antiretroviral (ARV) therapy (HAART) for most pregnant women for maternal control of HIV and prevention of mother-to-child transmission . Lopinavir/ritonavir (LPV/r) is one of the most common boosted protease inhibitor (PI) combinations used by pregnant women in the United States and continues to be the first-line choice for PI therapy for HIV-1-infected pregnant women in many clinical centres. Optimum dosing of PI-based regimens during pregnancy can be complicated by substantial changes in the pharmacokinetics of ARVs, which can be more pronounced during the third trimester of pregnancy. Alterations of gastrointestinal function during pregnancy may impair drug absorption.