Estimation of Drug Pharmacokinetics from Breast Feeding: A Simple Method Based on Meta-analysis
Oumar Aboubacar Alassane *
Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, Purpan University Hospital, Toulouse, France, Pharmacology and Pharmacogenetic Laboratory, University Institute of Cancer Oncopôle, Toulouse, France and HIV/TB Research and Training Center, University of Science, Techniques and Technologies in Bamako, Mali.
De Pablos-Martinez Carlos
Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, Purpan University Hospital, Toulouse, France.
Maiga Mamoudou
Northwestern University, Division of Infectious Diseases, Chicago, USA.
Dao Sounkalo
HIV/TB Research and Training Center, University of Science, Techniques and Technologies in Bamako, Mali.
Chatelut Etienne
Pharmacology and Pharmacogenetic Laboratory, University Institute of Cancer Oncopôle, Toulouse, France.
Gandia Peggy
Pharmacokinetics and Toxicology Laboratory, Federative Institute of Biology, Purpan University Hospital, Toulouse, France.
*Author to whom correspondence should be addressed.
Abstract
Background: In resource-limited settings, breastfeeding is the healthiest source of nutrition for newborns. For economic/cultural reasons, breastfeeding is the preferred option for the majority of mothers, including HIV-positive mothers.
Objective: The objective of this review is to document parameters characterizing antiretroviral therapy (ARV) diffusion into breast milk associated with the estimated ARV amount ingested by breastfed infant and clinical/biological abnormalities.
Data Source and Eligibility Criteria: Twenty seven (27) published articles on the aspects of Pharmacokinetic parameters on ARV diffusion into breast milk have shown a large variability without clear interpretation on drugs diffusion. Using PubMed and Embase, we conducted a search to identify all published studies at 2015 that characterized antiretroviral drug diffusion from mother to infant via breast milk. We identified 27 published studies that characterized antiretroviral drug passage from mother to infant (drug concentrations in mother’s milk and breastfed plasma). Information was sufficiently complete for inclusion in the present analysis for only six antiretroviral drugs.
Results: Finally, only data for nevirapine and efavirenz were exploitable because some of the studies found null or non-detectable levels, which were not suitable for simulations. Median (IQR) nevirapine CL/F were 0.022 (0.013-0.038) for newborns, 0.121 (0.116-0.125) for children and 0.056 (0.045-0.070) for mothers, all in L/h/kg. Efavirenz CL/F were 0.025 (0.016-0.039) for newborns, 0.273 (0.261-0.285) for children and 0.160 (0.153-0.167) for mothers, also in L/h/kg.
Conclusion: Pharmacokinetics parameters of efavirenz and nevirapine are important to be determined in breastfed newborns.
Keywords: Breast milk, antiretroviral drugs, newborn exposure.