A systematic review on maternal-to-infant transfer of drugs through breast milk during the treatment of malaria, tuberculosis, and neglected tropical diseases.

Publication date: Jul 01, 2023

Exclusive breastfeeding of infants under 6 months of age is recommended by the World Health Organization. In 2021, over 300 million combined incident cases of malaria, tuberculosis, and neglected tropical diseases (NTDs) were reported, predominantly in low-income countries. For many of the drugs used as first-line treatments for these conditions, there is limited knowledge on infant exposure through breastfeeding with poorly understood consequences. This review summarized available knowledge on mother-to-infant transfer of these drugs to inform future lactation pharmacokinetic studies. A list of first-line drugs was generated from the latest WHO treatment guidelines. Using standard online databases, 2 independent reviewers searched for eligible articles reporting lactation pharmacokinetics studies and extracted information on study design, participant characteristics, and the mathematical approach used for parameter estimation. A third reviewer settled any disagreements between the 2 reviewers. All studies were scored against the standardized “ClinPK” checklist for conformity to best practices for reporting clinical pharmacokinetic studies. Simple proportions were used to summarize different study characteristics. The most remarkable finding was the scarcity of lactation pharmacokinetic data. Only 15 of the 69 drugs we listed had lactation pharmacokinetics fully characterized. Most studies enrolled few mothers, and only one evaluated infant drug concentrations. Up to 66% of the studies used non-compartmental analysis to estimate pharmacokinetic parameters rather than model-based compartmental analysis. Unlike non-compartmental approaches, model-based compartmental analysis provides for dynamic characterization of individual plasma and breast milk concentration-time profiles and adequately characterizes variability within and between individuals, using sparsely sampled data. The “ClinPK” checklist inadequately appraised the studies with variability in the number of relevant criteria across different studies. A consensus is required on best practices for conducting and reporting lactation pharmacokinetic studies, especially in neglected diseases such as malaria, tuberculosis, and NTDs, to optimize treatment of mother-infant pairs.

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Concepts Keywords
Breastfeeding Breast
Conducting Compartmental
Pharmacokinetics Diseases
Tuberculosis Drugs


Type Source Name
disease MESH malaria
pathway KEGG Malaria
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH neglected diseases
disease MESH Infectious Diseases
pathway REACTOME Reproduction
drug DRUGBANK Stavudine
disease MESH morbidity
disease MESH infections
drug DRUGBANK Artemisinin
drug DRUGBANK Lumefantrine
drug DRUGBANK Piperaquine
drug DRUGBANK Quinine
drug DRUGBANK Rifampicin
drug DRUGBANK Isoniazid
drug DRUGBANK Pyrazinamide
drug DRUGBANK Ethambutol
disease MESH pulmonary tuberculosis
drug DRUGBANK Levofloxacin
drug DRUGBANK Trestolone
drug DRUGBANK Moxifloxacin
drug DRUGBANK Bedaquiline
drug DRUGBANK Linezolid
drug DRUGBANK Clarithromycin
disease MESH ulcers
disease MESH leprosy
drug DRUGBANK Melarsoprol
disease MESH African trypanosomiasis
pathway KEGG African trypanosomiasis
disease MESH parasitic infections
disease MESH leishmaniasis
pathway KEGG Leishmaniasis
disease MESH onchocerciasis
drug DRUGBANK Coenzyme M
drug DRUGBANK Gold
disease MESH Buruli ulcer
disease MESH Chagas disease
pathway KEGG Chagas disease
disease MESH echinococcosis
disease MESH mycetoma
disease MESH chromoblastomycosis
disease MESH mycoses
disease MESH scabies
disease MESH schistosomiasis
disease MESH taeniasis
disease MESH cysticercosis
disease MESH yaws
disease MESH rabies
disease MESH dengue
drug DRUGBANK Artemether
drug DRUGBANK Artesunate
drug DRUGBANK Amodiaquine
drug DRUGBANK Mefloquine
drug DRUGBANK Artenimol
drug DRUGBANK Sulfadoxine
drug DRUGBANK Pyrimethamine
drug DRUGBANK Pyronaridine
drug DRUGBANK Atovaquone
drug DRUGBANK Proguanil
drug DRUGBANK Chloroquine
drug DRUGBANK Doxycycline
drug DRUGBANK Primaquine
drug DRUGBANK Clindamycin
drug DRUGBANK Kanamycin
drug DRUGBANK Capreomycin
drug DRUGBANK Streptomycin
drug DRUGBANK Clofazimine
drug DRUGBANK Delamanid
drug DRUGBANK Meropenem
drug DRUGBANK Imipenem
drug DRUGBANK Cilastatin
drug DRUGBANK Amikacin
drug DRUGBANK Clavulanic acid
drug DRUGBANK Ethionamide
drug DRUGBANK Protionamide
drug DRUGBANK Benznidazole
drug DRUGBANK Nifurtimox
drug DRUGBANK Albendazole
drug DRUGBANK Mebendazole
drug DRUGBANK Praziquantel
drug DRUGBANK Triclabendazole
drug DRUGBANK Pentamidine
drug DRUGBANK Fexinidazole
drug DRUGBANK Suramin
drug DRUGBANK Sodium stibogluconate
drug DRUGBANK Meglumine antimoniate
drug DRUGBANK Amphotericin B
drug DRUGBANK Miltefosine
drug DRUGBANK Paromomycin
drug DRUGBANK Dapsone
disease MESH Lymphatic filariasis
drug DRUGBANK Ivermectin
drug DRUGBANK Trimethoprim
drug DRUGBANK Sulfamethoxazole
drug DRUGBANK Minocycline
drug DRUGBANK Sulfate ion
drug DRUGBANK Posaconazole
drug DRUGBANK Voriconazole
drug DRUGBANK Itraconazole
drug DRUGBANK Fluorouracil
drug DRUGBANK Thiabendazole
drug DRUGBANK Ketoconazole
drug DRUGBANK Fluconazole
drug DRUGBANK Terbinafine
disease MESH river blindness
drug DRUGBANK Niclosamide
drug DRUGBANK Azithromycin
drug DRUGBANK Indoleacetic acid
drug DRUGBANK Cysteamine
drug DRUGBANK Ademetionine
drug DRUGBANK Pentaerythritol tetranitrate

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