The Quantitative Sciences team at the Gates Foundation engaged the START Center to conduct a scoping review to map the existing literature on levonorgestrel, a synthetic progestin, in populations with pathophysiology theorized or understood to impact drug pharmacokinetics (e.g. undernutrition, liver disease, female reproductive tract abnormalities, gastrointestinal illnesses) and identify relevant PK data and gaps in the literature.
The Qualitative Sciences team is broadly interested in physiologically based pharmacokinetic (PBPK) models, hormonal contraceptives, and reproductive modeling. Through exploratory searches on these topics, the START team explored the extent to which PBPK models are tailored for populations in low-and middle-income countries.
The START team searched PubMed, Embase, Global Index Medicus, and the U.S. Drugs@FDA database, finding seventeen articles covering eight special conditions included in this review. Results revealed an overall scarcity of levonorgestrel PK data for multiple special population groups, highlighting an abundant need to learn more about the potential impacts of altered physiology on drug absorption, distribution, metabolism, and excretion. Limited data suggests potentially different PK profiles for levonorgestrel among populations with undernutrition and gastrointestinal illness, however more research is needed.
Final deliverables included a report summarizing the scoping review findings and PK parameters in different special populations. Two supplemental files, an excel data extraction sheet summarizing article metadata, methodology and pharmacokinetic findings, and a document with article figures and tables were also submitted. A final presentation took place over Zoom in February 2025.
