Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved]
Background: Data surrounding the exposure of the breastfed infant to drugs and any associated risks are sparse. Drugs usually are transferred to milk in small quantities, and many have been used without obviously noticeable infant toxicity for many years – this lack of a ‘safety signal’ has further...
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| Format: | Article |
| Language: | English |
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Wellcome
2023-08-01
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| Series: | Wellcome Open Research |
| Subjects: | |
| Online Access: | https://wellcomeopenresearch.org/articles/8-12/v2 |
| _version_ | 1827813698733867008 |
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| author | Ritah Nakijoba Catriona Waitt Francis Williams Ojara Aida Nakayiwa Kawuma Jacqueline Kyeyune Jovia C. Tabwenda Simon Peter Asiimwe Christine Turyahabwe Johnson Magoola Clifford George Banda Allan Buzibye Barbara Castelnuovo |
| author_facet | Ritah Nakijoba Catriona Waitt Francis Williams Ojara Aida Nakayiwa Kawuma Jacqueline Kyeyune Jovia C. Tabwenda Simon Peter Asiimwe Christine Turyahabwe Johnson Magoola Clifford George Banda Allan Buzibye Barbara Castelnuovo |
| author_sort | Ritah Nakijoba |
| collection | DOAJ |
| description | Background: Data surrounding the exposure of the breastfed infant to drugs and any associated risks are sparse. Drugs usually are transferred to milk in small quantities, and many have been used without obviously noticeable infant toxicity for many years – this lack of a ‘safety signal’ has further reduced the interest in studying mother-to-infant transfer of the drugs. In sub-Saharan Africa, pregnant women are at risk of Plasmodium falciparum infection, and one in four women have evidence of placental infection at the time of delivery. Artemisinin-based combination therapies (ACTs), primarily artemether-lumefantrine (AL), are the current first-line treatment for uncomplicated Plasmodium falciparum malaria, with the same dosing recommendations in breastfeeding women as those in the adult population. Dihydroartemisinin-piperaquine (DP) is routinely used as an alternative to AL in Uganda. However, lactation pharmacokinetics (PK) of ACTs are unknown. Pharmacokinetic characterization of anti-malarial transfer to breast milk and breastfed infants is crucial in understanding the potential consequences to the infant, in terms of therapeutic- and prophylactic effects as well as potential toxicity. Methods: This observational study will enroll 30 mother-infant pairs, and aims to characterize the breastmilk transfer of antimalarial medications (AL and DP) to infants when these ACTs are administered to mothers as part of treatment for uncomplicated malaria. In addition, we will assess the mental health of the breastfeeding mothers enrolled as well as the well-being of their children. PK samples of maternal blood, breastmilk and breastfeeding infant’s blood will be obtained at specific times points. Pharmacokinetic data will be analyzed using a population pharmacokinetic approach. Conclusions: We anticipate that findings from this research will guide to develop a PK model describing lumefantrine and piperaquine disposition and will provide a framework to foster other lactation pharmacokinetic studies in different disease areas. |
| first_indexed | 2024-03-11T23:35:48Z |
| format | Article |
| id | doaj.art-37d2ebd2887943f482a12d0915d1782f |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-03-11T23:35:48Z |
| publishDate | 2023-08-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-37d2ebd2887943f482a12d0915d1782f2023-09-20T01:00:00ZengWellcomeWellcome Open Research2398-502X2023-08-01822003Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved]Ritah Nakijoba0https://orcid.org/0000-0002-6626-0329Catriona Waitt1https://orcid.org/0000-0003-0134-5855Francis Williams Ojara2Aida Nakayiwa Kawuma3https://orcid.org/0000-0001-7975-0178Jacqueline Kyeyune4Jovia C. Tabwenda5Simon Peter Asiimwe6Christine Turyahabwe7Johnson Magoola8Clifford George Banda9https://orcid.org/0000-0002-0757-5259Allan Buzibye10Barbara Castelnuovo11Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaMalawi-Liverpool-Wellcome Clinical Research Programme, Blantyre, 265, MalawiInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, 256, UgandaBackground: Data surrounding the exposure of the breastfed infant to drugs and any associated risks are sparse. Drugs usually are transferred to milk in small quantities, and many have been used without obviously noticeable infant toxicity for many years – this lack of a ‘safety signal’ has further reduced the interest in studying mother-to-infant transfer of the drugs. In sub-Saharan Africa, pregnant women are at risk of Plasmodium falciparum infection, and one in four women have evidence of placental infection at the time of delivery. Artemisinin-based combination therapies (ACTs), primarily artemether-lumefantrine (AL), are the current first-line treatment for uncomplicated Plasmodium falciparum malaria, with the same dosing recommendations in breastfeeding women as those in the adult population. Dihydroartemisinin-piperaquine (DP) is routinely used as an alternative to AL in Uganda. However, lactation pharmacokinetics (PK) of ACTs are unknown. Pharmacokinetic characterization of anti-malarial transfer to breast milk and breastfed infants is crucial in understanding the potential consequences to the infant, in terms of therapeutic- and prophylactic effects as well as potential toxicity. Methods: This observational study will enroll 30 mother-infant pairs, and aims to characterize the breastmilk transfer of antimalarial medications (AL and DP) to infants when these ACTs are administered to mothers as part of treatment for uncomplicated malaria. In addition, we will assess the mental health of the breastfeeding mothers enrolled as well as the well-being of their children. PK samples of maternal blood, breastmilk and breastfeeding infant’s blood will be obtained at specific times points. Pharmacokinetic data will be analyzed using a population pharmacokinetic approach. Conclusions: We anticipate that findings from this research will guide to develop a PK model describing lumefantrine and piperaquine disposition and will provide a framework to foster other lactation pharmacokinetic studies in different disease areas.https://wellcomeopenresearch.org/articles/8-12/v2malaria breastmilk pharmacokinetics Africa lactationeng |
| spellingShingle | Ritah Nakijoba Catriona Waitt Francis Williams Ojara Aida Nakayiwa Kawuma Jacqueline Kyeyune Jovia C. Tabwenda Simon Peter Asiimwe Christine Turyahabwe Johnson Magoola Clifford George Banda Allan Buzibye Barbara Castelnuovo Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved] Wellcome Open Research malaria breastmilk pharmacokinetics Africa lactation eng |
| title | Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved] |
| title_full | Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved] |
| title_fullStr | Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved] |
| title_full_unstemmed | Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved] |
| title_short | Pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs: An observational pharmacokinetic study [version 2; peer review: 2 approved] |
| title_sort | pharmacokinetics of antimalarial drugs used to treat uncomplicated malaria in breastfeeding mother infant pairs an observational pharmacokinetic study version 2 peer review 2 approved |
| topic | malaria breastmilk pharmacokinetics Africa lactation eng |
| url | https://wellcomeopenresearch.org/articles/8-12/v2 |
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