%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Cressey, T. R.
%A Urien, S.
%A Capparelli, E. V.
%A Best, B. M.
%A Buranabanjasatean, S.
%A Limtrakul, A.
%A Rawangban, B.
%A Sabsanong, P.
%A Treluyer, J. M.
%A Jourdain, Gonzague
%A Stek, A.
%A Lallemant, Marc
%A Mirochnick, M.
%T Impact of body weight and missed doses on lopinavir concentrations with standard and increased lopinavir/ritonavir doses during late pregnancy
%D 2015
%L fdi:010063967
%G ENG
%J Journal of Antimicrobial Chemotherapy
%@ 0305-7453
%K HIV ; pharmacokinetics ; Thailand ; USA
%K THAILANDE ; ETATS UNIS
%M ISI:000350210800030
%N 1
%P 217-224
%R 10.1093/jac/dku367
%U https://www.documentation.ird.fr/hor/fdi:010063967
%> https://www.documentation.ird.fr/intranet/publi/2015/04/010063967.pdf
%V 70
%W Horizon (IRD)
%X 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 (similar to 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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