A Systematic Review of Published Physiologically Based Pharmacokinetic Models for Drug Excretion Into Human Breastmilk: Knowledge Gaps and Opportunities to Optimize Reporting and Modeling Practices
In brief
Only 18% of lactation PBPK studies report all key modeling details
A review of 26 physiologically based pharmacokinetic papers covering 54 drugs found that just four of the 22 recommended reporting items were consistently provided, meaning only 18% met full transparency standards. Most models used whole-body structures and half assumed perfusion-limited milk excretion, but gaps in clinical data and physiology limit confidence. Better, standardized reporting is needed before these models can reliably guide infant exposure assessments.
- Journal
- CPT: pharmacometrics & systems pharmacology (Q1)
- Published
- 1 August 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Joshua Kiptoo, Davies Otieno, Kenta Yoshida, Neel Deferm, Aida Nakayiwa Kawuma, Francis Williams Ojara, et al.
- PMID
- 42571641
- DOI
- 10.1002/psp4.70321
Why clinicians should know about it
- Picked for Pharmacology (medical) (paper of the day, 10 August 2026): PBPK models predict drug excretion into human breastmilk
Abstract
Physiologically based pharmacokinetic (PBPK) modeling is increasingly used to predict infant exposure to medications via breast milk. Existing guidance on reporting of PBPK modeling analyses is unstructured and nonbinding to researchers. We evaluated reporting practices and modeling approaches in published PBPK modeling studies. A systematic search was conducted across three online databases. Studies published through March 2025 that leveraged PBPK to evaluate milk drug excretion and infant exposure were included. We developed a 22-item structured data abstraction tool-Lactation PBPK Model Reporting Checklist (LAC-PBPK). Study findings were reported using descriptive and narrative analyses. Twenty-six published studies modeling 54 medications met the inclusion criteria. Using the data abstraction tool, only 4 (18%) of reporting domains were reported in all studies. These include the drug modeled, choice of mammary distribution model, context of PBPK modeling (model purpose), and the modeling platform. Most studies (88.4%) implemented whole-body PBPK model structure, with one-half (53%) assuming perfusion-rate-limited milk excretion. Assumptions reflect modeling limitations, primarily due to inadequate reporting in clinical lactation studies and knowledge gaps in infant and mammary physiology. PBPK models can support mechanistic assessment of drug excretion into breast milk, but confidence in model outputs depends on intended use, data availability, and transparent reporting. This highlights the need for a prioritized, fit-for-purpose lactation PBPK reporting framework. From a regulatory perspective, transparent reporting and cautious selection of approaches for estimating infant milk intake, model performance evaluation, physiological extrapolation, and parameter uncertainty analyses are essential to ensure reproducibility and confidence in PBPK-informed infant exposure assessment.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.