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J Antimicrob Chemother. 2015 Jan;70(1):217-24. doi: 10.1093/jac/dku367. Epub 2014 Sep 25.

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

Author information

1
Program for HIV Prevention and Treatment (IRD UMI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand Harvard School of Public Health, Boston, MA, USA Institut de Recherché pour le Développement (IRD), UMI 174-PHPT, Marseille, France tim.cressey@phpt.org.
2
EA-3620 University Paris Descartes and CIC-0901 Inserm, Paris, France Hôpital Cochin, Assistance Publique-Hopitaux de Paris, Paris, France Unité de Recherche clinique, AP-HP, Hôpital Tarnier, Paris, France.
3
University of California San Diego, La Jolla, CA, USA.
4
Mae Chan Hospital, Mae Chan, Thailand.
5
Nakornping Hospital, Chiang Mai, Thailand.
6
Nopparat Rajathanee Hospital, Bangkok, Thailand.
7
Samutprakarn Hospital, Samutprakarn, Thailand.
8
Program for HIV Prevention and Treatment (IRD UMI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand Harvard School of Public Health, Boston, MA, USA Institut de Recherché pour le Développement (IRD), UMI 174-PHPT, Marseille, France.
9
University of Southern California, Los Angeles, CA, USA.
10
Boston University, Boston, MA, USA.

Abstract

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.

KEYWORDS:

HIV; Thailand; USA; pharmacokinetics

PMID:
25261418
PMCID:
PMC4267507
DOI:
10.1093/jac/dku367
[Indexed for MEDLINE]
Free PMC Article

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