# Unbound piperaquine pharmacokinetic exposure in Ugandan pregnant women and children receiving malaria chemoprevention

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $201,875

## Abstract

Project Summary
Malaria remains one of the most challenging infectious diseases in the world causing roughly 200 million cases
and half a million deaths annually. As the most vulnerable populations, pregnant women and children are
recommended for preventive treatment. Our program has addressed fundamental questions as to how
pregnancy and childhood development impact the pharmacokinetics (PK) and pharmacodynamics (PD) of
dihydroartemisinin (DHA)-piperaquine (PQ), the preferred artemisinin-based combination therapy for
chemoprevention. We demonstrated nearly a 40 percent reduction in PQ exposure in pregnant women and
children compared to nonpregnant adults. However, considering PQ is highly protein bound, alteration of
protein binding during pregnancy and childhood development may impact fraction of unbound PQ that is free to
transverse biological membranes and exert pharmacological effect at target sites, therefore, dose adjustment
should weigh in unbound PQ exposure. Although total PQ exposure has been well studied, unbound free PQ
exposure remains to be unexplored. In this proposal, we will evaluate the unbound PQ pharmacokinetic
exposure in pregnant women and children, leveraging resource from the existing clinical studies. We
developed a sensitive method to measure free PQ at as low as 20 pg/mL and will explore two dimensional
liquid chromatography (2D-LC) for unbound PQ separation and quantitation with a smaller plasma sample
volume. Finally, we will also explore PK/PD modelling with unbound PQ and identify the unbound PQ
concentrations associated with malaria protection. The knowledge gained on unbound PQ exposure is
expected to optimize interpretation of total PQ exposure to inform treatment guidelines for pregnant women
and children. The novel 2D-LC method, if succeeded, can be used as a general method for analysis of other
unbound drugs.

## Key facts

- **NIH application ID:** 10439896
- **Project number:** 5R21AI153848-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Liusheng Huang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2021-06-28 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439896

## Citation

> US National Institutes of Health, RePORTER application 10439896, Unbound piperaquine pharmacokinetic exposure in Ugandan pregnant women and children receiving malaria chemoprevention (5R21AI153848-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439896. Licensed CC0.

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