Fosamprenavir with ritonavir pharmacokinetics during pregnancy

Ahizechukwu C. Eke, Jiajia Wang, Khadija Amin, David E. Shapiro, Alice Stek, Elizabeth Smith, Nahida Chakhtoura, Michael Basar, Kathleen George, Katherine M. Knapp, Esaú C. João, Kittipong Rungruengthanakit, Edmund Capparelli, Sandra Burchett, Mark Mirochnick, Brookie M. Best, Linda Bettica, Charmane Calilap-Bernardo, Arlene Bardeguez, Shelley BuschurChivon Jackson, Mary Paul, Philip La Russa, Claudia Florez, Patricia Bryan, Monica Stone, Debra McLaud, Christina Yarrington, Diana Clarke, Nagamah Deygoo, William Borkowsky, Françoise Kamer, La Shonda Spencer, James Homans, Esau C. Joao, Camille Medeiros Braga, Marcelo H. Losso, Silvina A. Ivalo, Alejandro Hakim, Julie Schmidt, Maureen McNichols, Mariam Aziz, Jaime G. Deville, Karin Nielsen, Bonnie Ank, Katherine M. Knapp, Nina Sublette, Edwin Thorpe

Research output: Contribution to journalArticle

Abstract

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 μg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0–12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P< 0.001]) while its apparent oral clearance was higher (GMR, 1.68 [CI, 1.38 to 2.03] [P< 0.001]) in the third trimester than postpartum. Similarly, the ritonavir AUC0–12 was lower in the second (GMR, 0.51 [CI, 0.28 to 0.91] [P= 0.09]) and third (GMR, 0.72 [CI, 0.55 to 0.95] [P= 0.005]) trimesters than postpartum, while its apparent oral clearance was higher in the second (GMR, 1.98 [CI, 1.10 to 3.56] [P= 0.06]) and third (GMR, 1.38 [CI, 1.05 to 1.82] [P= 0.009]) trimesters than postpartum. The amprenavir area under the curve exceeded the target for 6/8 (75%) women in the 2nd trimester, 18/28 (64%) in the 3rd trimester, and 19/22 (86.4%) postpartum, and the trough concentrations (Cmin) of amprenavir were 4- to 16-fold above the mean amprenavir-protein-adjusted 50% inhibitory concentration (IC50) of 0.146 μg/ml. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy than postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression.

Original languageEnglish (US)
Article numbere02260
JournalAntimicrobial agents and chemotherapy
Volume64
Issue number4
DOIs
StatePublished - 2020

Keywords

  • AIDS
  • Amprenavir
  • Fosamprenavir
  • Human immunodeficiency virus
  • Pharmacokinetics
  • Postpartum
  • Pregnancy
  • Ritonavir

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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  • Cite this

    Eke, A. C., Wang, J., Amin, K., Shapiro, D. E., Stek, A., Smith, E., Chakhtoura, N., Basar, M., George, K., Knapp, K. M., João, E. C., Rungruengthanakit, K., Capparelli, E., Burchett, S., Mirochnick, M., Best, B. M., Bettica, L., Calilap-Bernardo, C., Bardeguez, A., ... Thorpe, E. (2020). Fosamprenavir with ritonavir pharmacokinetics during pregnancy. Antimicrobial agents and chemotherapy, 64(4), [e02260]. https://doi.org/10.1128/AAC.02260-19