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Webinar

MIDD’s Growing Role in Global Health: A Case Study of Primaquine Exposures in Lactating Women and Breastfed Infants

Date: Thursday, May 22, 2025

Time: 11am-12pm ET

Solutions: Early Clinical, Late Clinical, Regulatory

Services: Simcyp™ PBPK Modeling Services

Products: Simcyp™

Summary

Model-informed drug development (MIDD) is increasingly adopted to support global health equity by providing guidance on the safe use of medications in lactating women and their nursing infants. In this webinar, we will explore how MIDD enhances clinical lactation studies to support more informed decision-making regarding the safety of administering medication to lactating mothers.

Plasmodium vivax malaria remains a global health issue, with 6.9 million cases in 2022.1 Primaquine is a drug used to prevent relapse and treat P. vivax malaria (radical cure). Until November 2024, when the last WHO guidelines for malaria were published, its use was restricted for lactating women if their children were < 6 months, fearing infant harm from exposure via breast milk. A major change was implemented in the last guideline, adjusting the restriction age to < 1 month. This was supported by a clinical lactation study, which was conducted to measure primaquine concentration in breastmilk and in nursing infants > 1 month old. Results showed that primaquine concentrations in infant plasma were extremely low, with no measurable effects on infants.3

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Many women in malaria endemic communities live far from healthcare facilities. The postpartum period is an operationally strategic time to provide radical cure for women who have vivax malaria in pregnancy, but primaquine is still not recommended for women breastfeeding neonates. Planned follow-up studies in the neonatal period have been delayed by concerns about neonatal safety by ethical approval boards.2 Physiologically-based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modeling approaches were used to complement the clinical study by predicting risk from drug exposure in breast milk and extrapolating data to neonates < 1 month old.4,5

The modeling results predicted negligible risk, suggesting that studies during this physiologically vulnerable time could safely be conducted, and that expansion of radical cure to this group is likely possible.

Key Takeaways:

Global health impact: MIDD can enhance global health equity by helping optimize clinical study design to make the most of scarce funding, and to extrapolate data from studied to unstudied scenarios.

Specific population considerations: Special attention is needed for underserved populations such as lactating women and neonates who are frequently excluded from clinical studies due to safety concerns. Modeling approaches like PBPK and PopPK help estimate drug exposure and hence assess predicted safety , supporting evidence-based study design and drug dosing considerations.

Policy implications: Quantitative guidance, informed by both clinical data and predictive modeling, can assist with decision-making about the restrictions on primaquine use in lactating women, reducing the risk of recurrent malaria for mothers caring for their infants, and strengthening global malaria control strategies.

Relevance to drug development: Considering the increased call for drug developers to take into account the unique physiology of children, and pregnant and lactating women early in drug development, the strategy described here (clinical lactation study complemented by modeling) can be instrumental in the industry setting.

Speakers:

Karen Rowland, SVP, Client & Regulatory Strategy at Certara
Karen Rowland-Yeo, PhD

SVP, Client & Regulatory Strategy, Certara

Joel Tarning, PhD

Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK

Mellie Gilder, MD

Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK

Nada Abla Geiser, PharmD, PhD

Director, Drug Disposition & PBPK Modeling, Medicines for Malaria Venture

References:

  1.  WHO. World malaria report 2023. Geneva: World Health Organization; 2023.
  2. Abla, N., Marrast, A.C., Jambert, E. et al. Addressing health equity for breastfeeding women: primaquine for Plasmodium vivax radical cure. Malar J 23, 287 (2024).
  3. Gilder ME, Hanpithakphong W, Hoglund RM, Tarning J, Win HH, Hilda N, Chu CS, Bancone G, Carrara VI, Singhasivanon P, White NJ, Nosten F, McGready R. Primaquine Pharmacokinetics in Lactating Women and Breastfed Infant Exposures. Clin Infect Dis. 2018 Sep 14;67(7):1000-1007. doi: 10.1093/cid/ciy235. PMID: 29590311; PMCID: PMC6137118.
  4. Wattanakul T, Gilder ME, McGready R, Hanpithakpong W, Day NPJ, White NJ, Nosten F, Tarning J, Hoglund RM. Population pharmacokinetic modelling of primaquine exposures in lactating women and breastfed infants. Nat Commun. 2024 May 8;15(1):3851. doi: 10.1038/s41467-024-47908-y. PMID: 38719803; PMCID: PMC11078975.
  5. Pan X, Abduljalil K, Almond LM, Pansari A, Yeo KR. Supplementing clinical lactation studies with PBPK modeling to inform drug therapy in lactating mothers: Prediction of primaquine exposure as a case example. CPT Pharmacometrics Syst Pharmacol. 2024 Mar;13(3):386-395. doi: 10.1002/psp4.13090. Epub 2023 Dec 12. PMID: 38084656; PMCID: PMC10941563.

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