Background: Globally, more than half of women take medicines whilst breastfeeding. Data concerning the exposure of the breastfed infant to drugs and any related risks are sparce. Lactation studies are only rarely performed close to licensing for medicines anticipated to be widely used in women of childbearing age. Medicines taken by breastfeeding mothers on tuberculosis (TB) treatment can be transferred to the breastfed infant. Potential effects of anti-tuberculosis medicines on nursing infants are not well understood. Similarly, women face mental health challenges while taking medications, including postpartum depression, hence the need to assess the psychological behavior of a breastfeeding woman. Potential risks are the development of adverse drug effects in the breastfed infant and selection for resistance, whereas potential benefits might include exposure to potentially prophylactic concentrations of the drug. Pharmacokinetic studies are therefore necessary to understand this situation fully.
Methods: This study will enroll 20 mothers receiving first-line anti-tuberculosis medicines, together with their breastfed infants, with the aim of characterizing the breastmilk transfer of the medicines from the mother to the infants. Samples of maternal blood, breastmilk, and breastfeeding infant's blood will be obtained at specific time points for bioanalysis of drug concentrations. Pharmacokinetic data will be analyzed using a population pharmacokinetic approach. Additionally, the study will assess the psychological status of breastfeeding women and the well-being of their infants. Maternal depression is linked to long-term negative consequences for the infant's physiological regulation, poor growth-promoting setting for the infants, and inappropriate interactive conduct, characterized by low compassion, constrained range of emotional expression, and varying provision of the infant's budding engagement.
Conclusions: This study will provide the first systematic characterization of mother-to-infant transfer of first-line anti-tuberculosis medicines through breast milk. A mathematical pharmacokinetics model characterizing plasma-to-breastmilk transfer of rifampicin, isoniazid, ethambutol, and pyrazinamide will be developed and used to characterize infant exposure through breast milk. Our findings will contribute towards treatment optimization in breastfeeding and provide a framework to foster other lactation pharmacokinetic studies.
Keywords: Africa; Tuberculosis; breastmilk pharmacokinetics; lactation.
Pharmacokinetics of drugs used to treat drug-sensitive tuberculosis in breastfeeding mother-infant pairs: An observational pharmacokinetic study. Tuberculosis drug exposure in the breastfed infant may be clinically important. tuberculosis drug exposure in the breastfed infant may be clinically important. The aims of the study are; To define the transfer of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol to the breastfed infant, and to determine the area under the concentration-time curve (AUC), clearance, and volume of distribution of these drugs. Understanding infant exposure to anti-tuberculosis drugs is important to inform on potential risks and benefits to the infant. Measuring drug concentrations directly in the infant is the best way to fully understand infant exposure and enable informed prediction of infant exposure. We have proposed a model-based population pharmacokinetics analysis approach for the characterization of changes in drug concentrations across time. Population analysis will enable a joint analysis of data from multiple participants, describing both the typical population- and individual-specific profiles. Model-based population analysis offers several advantages over the more commonly used non-compartmental analysis: it can be used for predictions and simulations and for intensive and sparse sampling. We anticipate that findings from this research will enable a clear description of optimal use of drug-sensitive tuberculosis drugs in breastfeeding mothers, will enable the development of clear patient information materials and will provide a framework to foster other pharmacokinetic lactation studies in different disease areas.
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