Format

Send to

Choose Destination
J Pharmacol Exp Ther. 2018 Jul 9. pii: jpet.118.249938. doi: 10.1124/jpet.118.249938. [Epub ahead of print]

Efavirenz and Lopinavir Levels in HIV-infected Women and their Nursing Infants, in Mali.

Author information

1
Universite des Sciences des Techniques et des Technologies de Bamako; aao@icermali.org.
2
Department pediatric Hospital Gabriel Toure.
3
Universite des Sciences, des Techniques et des Technologies de Bamako.
4
Northwestern University, Center for Global Health, Chicago.
5
Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, Purpan.
6
the Common Reference Health Center V.
7
INSERM UMR 1037 Pharmacology, Laboratory, University Institute of Cancer Oncopole.
8
Universite des Sciences des Techniques et des Technologies de Bamako.

Abstract

Limited data are currently available on antiretroviral pharmacokinetics in breast milk and in breastfed infants' blood. To explore these parameters in patients, in Mali, we measured plasma antiretroviral levels in HIV infected mothers and their breastfed infants over 6 months. We analyzed specifically, plasma's efavirenz and lopinavir concentrations in mothers living with HIV and their breastfed infants. Blood samples were collected at delivery and at month 1, 3 and 6 postpartum. Efavirenz and lopinavir concentrations were measured by LC/MS/MS. HIV-1 RNA load was measured by Abbott M2000RT at delivery and 6-months post-partum for mothers and at 3 and 6 months post-birth for infants. The median duration of ART at inclusion was 57 (0-168) months. The median EFV ratio of infant plasma/maternal plasma was 0.057 at month 1; 0.072 at month 3 and 0.048 at month 6. During the study period, the median breast milk/maternal plasma ratio (BM:MP) of efavirenz was 1.16 (0.96-20.62), which corresponds to a relative infant dose of 2.46% of the recommended weight-adjusted pediatric efavirenz dose at month 6. The CL/F infant EFV was 0.146 L/h/kg at months 6. All LPV infants' plasma concentrations were undetectable. No drug-related adverse reaction or toxicity was observed in any of the infants. The two women who presented a viral load >50 copies/mL at month-6 had undetectable plasma drug concentrations at the same period. This study showed that breastfed infants got a low level of efavirenz but not lopinavir from their treated mothers.

KEYWORDS:

HPLC; antiretrovirals; clinical pharmacokinetics; clinical pharmacology; developmental pharmacology; drug analysis; membrane permeability; sulfonylureas; toxicokinetics

PMID:
29986950
DOI:
10.1124/jpet.118.249938
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center