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Impact of body weight and missed doses on lopinavir concentrations with standard and increased lopinavir/ritonavir doses during late pregnancy

  • Author(s): Cressey, TR
  • Urien, S
  • Capparelli, EV
  • Best, BM
  • Buranabanjasatean, S
  • Limtrakul, A
  • Rawangban, B
  • Sabsanong, P
  • Treluyer, JM
  • Jourdain, G
  • Stek, A
  • Lallemant, M
  • Mirochnick, M
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267507/
No data is associated with this publication.
Abstract

© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: To assess the influence of body weight and missed doses on lopinavir pharmacokinetics with standard and increased doses of lopinavir/ritonavir melt extrusion tablets during late pregnancy. Patients and methods: Lopinavir concentration data during the third trimester of pregnancy were pooled from clinical trials in Thailand (NCT00409591) and the USA (NCT00042289). A total of 154 HIV-infected pregnant women receiving either 400/100 mg (standard) or 600/150 mg (increased) twice daily had lopinavir plasma concentration data available. Population parameters were estimated using non-linear mixed-effects regression models. Monte Carlo simulations were performed to estimate the probability of achieving target lopinavir trough concentrations (>1.0 mg/L) with standard and increased doses of lopinavir/ritonavir during pregnancy. Results: The median (range) age, weight and gestational age were 28 years (18-43), 62 kg (45-123) and 33 weeks (29-38), respectively. Body weight influenced lopinavir oral clearance (CL/F) and volume of distribution (V/F). Population estimates of lopinavir CL/F and V/F were 6.21 L/h/70 kg and 52.6 L/70 kg, respectively. Based on simulations, the highest risk of subtherapeutic trough concentrations was for women weighing >100 kg using the standard dose (∼7%), while the risk was <2% with the 600/150 mg dose for women weighing 40-130 kg. After a missed dose, 61% of women have lopinavir concentrations below target prior to the next dose with the standard dose compared with 42% with the increased dose. Conclusions: Standard dosing provides adequate lopinavir trough concentrations for the majority of pregnant women but increased doses may be preferable for women weighing >100 kg and with a history of lopinavir/ritonavir use and/or adherence issues.

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