We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment.
- Authors
Bouillon-Pichault, Marion; Jullien, Vincent; Azria, Elie; Pannier, Emmanuelle; Firtion, Ghislaine; Krivine, Anne; Compagnucci, Alexandra; Taulera, Olivier; Finkielsztejn, Laurent; Chhun, Stéphanie; Pons, Gérard; Launay, Odile; Treluyer, Jean-Marc
- Abstract
Objectives To investigate the possible necessity of an increase in lopinavir dose during pregnancy in order to achieve the concentrations previously defined as predictive of virological efficacy. Patients and methods Lopinavir pharmacokinetics were investigated by a population approach performed on 145 HIV-infected women, including 74 pregnant women. The final model was used to determine the probability of achievement of the target trough concentrations by Monte Carlo simulations. Results The typical population estimates (inter-individual variability %) of apparent clearance (CL/F) and volume of distribution were 4.38 L/h (24%) and 58.4 L (59%), respectively. Pregnancy associated with a gestational age >15 weeks and delivery were found to increase lopinavir CL/F by 39% and 58%, respectively. With the standard 400 mg twice-a-day regimen, the probability of reaching the 1 mg/L target trough concentration for protease inhibitor (PI)-naive patients was 99% and 96% for non-pregnant and pregnant women, respectively. An important decrease in the probability of achieving the 5.7 mg/L target trough concentration for salvage therapy was observed for non-pregnant women (55%), this decrease being even greater for pregnant women (21%). Raising the lopinavir dose to 600 mg twice daily increased these probabilities to 87% and 53% for non-pregnant and pregnant women, respectively. Conclusions Modification of the lopinavir dose is unlikely to be required for PI-naive pregnant women; however, in pregnant women who have previously received a PI, therapeutic drug monitoring and/or empirical increasing of the dose should be considered.
- Subjects
POPULATION health; PREGNANCY; ANTIRETROVIRAL agents; DRUG dosage; PHARMACOKINETICS; MEDICAL virology; DRUG efficacy; MATHEMATICAL models in medicine; HIV-positive women; MONTE Carlo method; PROTEASE inhibitors; DRUG monitoring
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2009, Vol 63, Issue 6, p1223
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkp123