Lopinavir protein binding in HIV-1-infected pregnant women
F T Aweeka, A Stek, B M Best, C Hu, D Holland, A Hermes, S K Burchett, J Read, M Mirochnick, E V Capparelli, International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1026s Protocol Team, Mark Mirochnick, Alice M Stek, Edmund Capparelli, Brookie M Best, Cheng-cheng Hu, Sandra K Burchett, Carol Elgie, Diane T Holland, Beth Sheeran, Janne Schiffhauer, James D Connor, Francesca Aweeka, Bradley W Kosel, Kathleen A Medvik, Elizabeth Smith, Jennifer S Read, Adolfo Gonzalez-Garcia, Mary Jo O'Sullivan, Gwendolyn B Scott, Liset Taybo, Seydi Vazquez-Bonilla, Alice Higgins, Diane Tose, Phil LaRusse, Andrew Hull, Mary Caffery, Linda Proctor, Stephen A Spector, Barbara Stechenberg, Eileen Theroux, Maripat Toye, Ann Marie Regan, Desiree Jones-Eaves, Stephen Pelton, Meg Sullivan, Katherine Luzuriaga, Sharon Cormier, Yvonne J Bryson, Maryanne Dillon, Audra Deveikis, Susan Marks, Jane Hitti, Ann Melvin, Michele Acker, Deb Goldman, Adriana Weinberg, Jill Davies, Carol Salbenblatt, Suzanne Paul, Sharon Nachman, Denise Ferraro, Jennifer Griffin, Paul Ogburn, Ana Melendrez, Françoise Kramer, LaShonda Spencer, Andrea Kovacs, F T Aweeka, A Stek, B M Best, C Hu, D Holland, A Hermes, S K Burchett, J Read, M Mirochnick, E V Capparelli, International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1026s Protocol Team, Mark Mirochnick, Alice M Stek, Edmund Capparelli, Brookie M Best, Cheng-cheng Hu, Sandra K Burchett, Carol Elgie, Diane T Holland, Beth Sheeran, Janne Schiffhauer, James D Connor, Francesca Aweeka, Bradley W Kosel, Kathleen A Medvik, Elizabeth Smith, Jennifer S Read, Adolfo Gonzalez-Garcia, Mary Jo O'Sullivan, Gwendolyn B Scott, Liset Taybo, Seydi Vazquez-Bonilla, Alice Higgins, Diane Tose, Phil LaRusse, Andrew Hull, Mary Caffery, Linda Proctor, Stephen A Spector, Barbara Stechenberg, Eileen Theroux, Maripat Toye, Ann Marie Regan, Desiree Jones-Eaves, Stephen Pelton, Meg Sullivan, Katherine Luzuriaga, Sharon Cormier, Yvonne J Bryson, Maryanne Dillon, Audra Deveikis, Susan Marks, Jane Hitti, Ann Melvin, Michele Acker, Deb Goldman, Adriana Weinberg, Jill Davies, Carol Salbenblatt, Suzanne Paul, Sharon Nachman, Denise Ferraro, Jennifer Griffin, Paul Ogburn, Ana Melendrez, Françoise Kramer, LaShonda Spencer, Andrea Kovacs
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
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Source: PubMed