Chronic administration of nevirapine during pregnancy: impact of pregnancy on pharmacokinetics
E V Capparelli, F Aweeka, J Hitti, A Stek, C Hu, S K Burchett, B Best, E Smith, J S Read, H Watts, S Nachman, E M Thorpe Jr, S A Spector, E Jimenez, W T Shearer, M Foca, M Mirochnick, PACTG 1026S Study Team, PACTG P1022 Study Team, Amanda Cotter, Gwendolyn B Scott, Edwin Thorpe Jr, Nina K Sublette, Pat Flynn, Stefan Hagmann, Murli Purswani, William Shearer, Mary E Paul, Hunter Hammill, Shelly Buscher, Andrew D Hull, Linda Proctor, Mary Caffery, Marc Foca, Alice Higgins, Anne Gershon, Arlene Bardeguez, Paul Palumbo, Deb Goldman, Michele Acker, Jane Hitti, Margaret A Keller, Marie Beall, Nicole Falgout, Spring Wettgen, Susan Marks, Audra Deveikis, Jennifer Griffin, Denise Ferraro, Silvia Muniz, Sharon Nachman, Jorge Gandía, Rodrigo Díaz, Elvia Pérez, Lourdes Angel, Ana M Melendrez, Yvonne Rodriguez, Françoise Kramer, LaShonda Spencer, Ruth Tuomala, Arlene Buck, Dorothy Pender, Diane W Wara, Maureen T Shannon, Marya G Zlatnik, Shantrice M Williams, Chitra S Mani, Debra J Ware, Karen Hickman, Barbara W Stechenberg, Mary Patricia Toye, E V Capparelli, F Aweeka, J Hitti, A Stek, C Hu, S K Burchett, B Best, E Smith, J S Read, H Watts, S Nachman, E M Thorpe Jr, S A Spector, E Jimenez, W T Shearer, M Foca, M Mirochnick, PACTG 1026S Study Team, PACTG P1022 Study Team, Amanda Cotter, Gwendolyn B Scott, Edwin Thorpe Jr, Nina K Sublette, Pat Flynn, Stefan Hagmann, Murli Purswani, William Shearer, Mary E Paul, Hunter Hammill, Shelly Buscher, Andrew D Hull, Linda Proctor, Mary Caffery, Marc Foca, Alice Higgins, Anne Gershon, Arlene Bardeguez, Paul Palumbo, Deb Goldman, Michele Acker, Jane Hitti, Margaret A Keller, Marie Beall, Nicole Falgout, Spring Wettgen, Susan Marks, Audra Deveikis, Jennifer Griffin, Denise Ferraro, Silvia Muniz, Sharon Nachman, Jorge Gandía, Rodrigo Díaz, Elvia Pérez, Lourdes Angel, Ana M Melendrez, Yvonne Rodriguez, Françoise Kramer, LaShonda Spencer, Ruth Tuomala, Arlene Buck, Dorothy Pender, Diane W Wara, Maureen T Shannon, Marya G Zlatnik, Shantrice M Williams, Chitra S Mani, Debra J Ware, Karen Hickman, Barbara W Stechenberg, Mary Patricia Toye
Abstract
Objectives: To determine the impact of pregnancy on the pharmacokinetics (PK) of nevirapine (NVP) during chronic dosing in HIV-infected women and appropriate NVP dosing in this population.
Methods: Twenty-six pregnant women participating in two open-label Pediatric AIDS Clinical Trials Group studies (P1022 and P1026S) were evaluated. Each patient received 200 mg NVP every 12 h and had PK evaluations during the second or third trimester; these evaluations were repeated postpartum. Paired maternal and cord blood NVP concentrations were collected at delivery in nine patients. Ante- and postpartum comparisons were made using paired t-tests and using a 'bioequivalence' approach to determine confidence interval (CI).
Results: The average NVP Area Under the Curve (AUC) was 56 +/- 13 mcg(*)h/mL antepartum and 61 +/- 15 mcg(*)h/mL postpartum. The typical parameters +/- standard error were apparent clearance (CL/F)=3.51 +/- 0.18 L/h and apparent volume of distribution (Vd/F)=121 +/- 19.8 L. There were no significant differences between antepartum and postpartum AUC or pre-dose concentrations. The AUC ratio was 0.90 with a 90% CI of the mean equal to 0.80-1.02. The median (+/- standard deviation) cord blood to maternal NVP concentration ratio was 0.91 +/- 0.90.
Conclusions: Pregnancy does not alter NVP PK and the standard dose (200 mg every 12 h) is appropriate during pregnancy.
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Source: PubMed