Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairs
Abstract Around 1.2 million women living with HIV give birth annually, majority of whom will breastfeed their infants while receiving antiretroviral therapy (ART). Lamivudine, a component of first‐line ART regimens crosses from maternal plasma to breast milk, with measurable concentrations in some b...
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| Format: | Article |
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Wiley
2024-11-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13274 |
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| author | Francis Williams Ojara Aida N. Kawuma Shadia Nakalema Isabella Kyohairwe Ritah Nakijoba Mohammed Lamorde Henry Pertinez Saye Khoo Catriona Waitt |
| author_facet | Francis Williams Ojara Aida N. Kawuma Shadia Nakalema Isabella Kyohairwe Ritah Nakijoba Mohammed Lamorde Henry Pertinez Saye Khoo Catriona Waitt |
| author_sort | Francis Williams Ojara |
| collection | DOAJ |
| description | Abstract Around 1.2 million women living with HIV give birth annually, majority of whom will breastfeed their infants while receiving antiretroviral therapy (ART). Lamivudine, a component of first‐line ART regimens crosses from maternal plasma to breast milk, with measurable concentrations in some breastfed infants. Wide variability in plasma‐to‐breast milk transfer has been reported within‐ or across studies, probably due to differences in sampling framework. This work sought to characterize the milk‐to‐plasma transfer of lamivudine, quantify inter‐patient variability and associated factors, and predict exposure of a breastfed infant. We explored data from an observational pharmacokinetic study that included 35 Ugandan mothers and their infants. Mothers received lamivudine doses of 150 mg twice daily or 300 mg once daily as part of their antiretroviral regimen. Pharmacokinetic sampling was undertaken across two visits approximately 8 weeks apart, providing 248 maternal plasma, 256 breast milk‐, and 151 infant blood concentrations, measured across a 24‐h sampling interval. A one‐compartmental model best described the plasma disposition of lamivudine, with first‐order absorption, interindividual variability on clearance and volume of distribution, and a proportional residual error model. A lag in time of plasma‐to‐breast milk drug accumulation was described using an effect compartment model with a milk‐to‐plasma ratio of 1.77. An estimated daily infant dose of 179.3 μg/kg (range: 125.8, 282.3) closely predicted the observed infant steady‐state concentrations and translated into 3.34% (2.13, 7.20) and 3.35% (1.10, 7.15) of the standard daily maternal dose in visits 1 and 2, respectively. The established modeling framework can be extended to other drugs. |
| format | Article |
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| institution | Kabale University |
| issn | 2163-8306 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj-art-f89184845f92439dbca8779d709274b02024-11-20T17:18:44ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062024-11-0113111978198910.1002/psp4.13274Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairsFrancis Williams Ojara0Aida N. Kawuma1Shadia Nakalema2Isabella Kyohairwe3Ritah Nakijoba4Mohammed Lamorde5Henry Pertinez6Saye Khoo7Catriona Waitt8Infectious Diseases Institute Makerere University College of Health Sciences Kampala UgandaInfectious Diseases Institute Makerere University College of Health Sciences Kampala UgandaInfectious Diseases Institute Makerere University College of Health Sciences Kampala UgandaInfectious Diseases Institute Makerere University College of Health Sciences Kampala UgandaInfectious Diseases Institute Makerere University College of Health Sciences Kampala UgandaInfectious Diseases Institute Makerere University College of Health Sciences Kampala UgandaDepartment of Pharmacology and Therapeutics University of Liverpool Liverpool UKDepartment of Pharmacology and Therapeutics University of Liverpool Liverpool UKInfectious Diseases Institute Makerere University College of Health Sciences Kampala UgandaAbstract Around 1.2 million women living with HIV give birth annually, majority of whom will breastfeed their infants while receiving antiretroviral therapy (ART). Lamivudine, a component of first‐line ART regimens crosses from maternal plasma to breast milk, with measurable concentrations in some breastfed infants. Wide variability in plasma‐to‐breast milk transfer has been reported within‐ or across studies, probably due to differences in sampling framework. This work sought to characterize the milk‐to‐plasma transfer of lamivudine, quantify inter‐patient variability and associated factors, and predict exposure of a breastfed infant. We explored data from an observational pharmacokinetic study that included 35 Ugandan mothers and their infants. Mothers received lamivudine doses of 150 mg twice daily or 300 mg once daily as part of their antiretroviral regimen. Pharmacokinetic sampling was undertaken across two visits approximately 8 weeks apart, providing 248 maternal plasma, 256 breast milk‐, and 151 infant blood concentrations, measured across a 24‐h sampling interval. A one‐compartmental model best described the plasma disposition of lamivudine, with first‐order absorption, interindividual variability on clearance and volume of distribution, and a proportional residual error model. A lag in time of plasma‐to‐breast milk drug accumulation was described using an effect compartment model with a milk‐to‐plasma ratio of 1.77. An estimated daily infant dose of 179.3 μg/kg (range: 125.8, 282.3) closely predicted the observed infant steady‐state concentrations and translated into 3.34% (2.13, 7.20) and 3.35% (1.10, 7.15) of the standard daily maternal dose in visits 1 and 2, respectively. The established modeling framework can be extended to other drugs.https://doi.org/10.1002/psp4.13274 |
| spellingShingle | Francis Williams Ojara Aida N. Kawuma Shadia Nakalema Isabella Kyohairwe Ritah Nakijoba Mohammed Lamorde Henry Pertinez Saye Khoo Catriona Waitt Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairs CPT: Pharmacometrics & Systems Pharmacology |
| title | Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairs |
| title_full | Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairs |
| title_fullStr | Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairs |
| title_full_unstemmed | Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairs |
| title_short | Population pharmacokinetic modeling of paired plasma–breast milk lamivudine data for estimation of infant exposure in breastfeeding mother–infant pairs |
| title_sort | population pharmacokinetic modeling of paired plasma breast milk lamivudine data for estimation of infant exposure in breastfeeding mother infant pairs |
| url | https://doi.org/10.1002/psp4.13274 |
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