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Pharmacokinetic-pharmacodynamic analysis of pyronaridine-artesunate in pregnant women with uncomplicated malaria

Terrmin

HT25

Beskrivning

Malaria presents a serious risk during pregnancy, contributing to adverse maternal and fetal outcomes. However, evidence to support safe and effective treatment in this population remains limited. Pyronaridine-artesunate is the most recent WHO-recommended artemisinin-based combination therapy (ACT) for treating uncomplicated Plasmodium falciparum and P. vivax malaria in adults and children. The PYRAPREG study assessed its efficacy and safety in pregnant women, including the appropriateness of standard adult dosing in this high-risk group.

In previous work, we characterized the whole-blood pharmacokinetics (PK) of pyronaridine in pregnant versus non-pregnant women with malaria, and explored the impact of HIV co-infection. Drug exposure was higher in pregnant women, especially in the third trimester, due to increased bioavailability, resulting in prolonged concentrations above the in vitro susceptibility threshold. We also identified a complex interplay between pregnancy status, malaria infection, and hemoglobin levels that influences drug distribution. While these findings indicate altered PK during pregnancy, they are not sufficient to determine whether dose adjustments are warranted. A longitudinal pharmacokinetic-pharmacodynamic (PK-PD) analysis is essential to evaluate the clinical impact and inform dosing recommendations.

This project aims to conduct a longitudinal PK-PD evaluation of pyronaridine-artesunate in pregnant women with malaria to:
1. Characterize drug effects on parasite clearance and recrudescence (main focus).
2. Assess the relationship between drug exposure and liver safety.
3. Perform simulations to explore potential dose adjustments based on the fixed-dose pyronaridine-artesunate tablet

Huvudområde

Farmaceutisk vetenskap

Ämne

Farmakometri

Typ

Beräkningsstudie

Företag

Uppsala University

Ort/Plats

Uppsala

Handledarens namn

Wendy Chu, Thomas Dorlo

Handledarens e-post

wan-yu.chu@uu.se

Institution

Institutionen för farmaci

Program

Masterprogram i läkemedelsmodellering

Kurs

Degree Project in Pharmaceutical Modeling within Pharmacometrics 45 c - 3FB029

Omfattning/hp

45hp