Pharmacokinetics of Artesunate in Malaria Patients
Author Information
Author(s): Simpson Julie A, Agbenyega Tsiri, Barnes Karen I, Perri Gianni Di, Folb Peter, Gomes Melba, Krishna Sanjeev, Krudsood Srivicha, Looareesuwan Sornchai, Mansor Sharif, McIlleron Helen, Miller Raymond, Molyneux Malcolm, Mwenechanya James, Navaratnam Visweswaran, Nosten Francois, Olliaro Piero, Pang Lorrin, Ribeiro Isabela, Tembo Madalitso, van Vugt Michele, Ward Steve, Weerasuriya Kris, Win Kyaw, White Nicholas J
Primary Institution: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, Australia
Hypothesis
The study investigates the population pharmacokinetics of intra-rectal artesunate and its relationship with parasitological responses in patients with moderately severe falciparum malaria.
Conclusion
The pharmacokinetic properties of dihydroartemisinin were affected only by gender and body weight, indicating that rectal artesunate is well absorbed in most patients with moderately severe malaria.
Supporting Evidence
- Patients with the lowest area under the DHA concentration curve did not have slower parasite clearance.
- Gender was associated with increased mean clearance of DHA.
- Weight was positively associated with the volume of distribution of DHA.
- Pharmacokinetic properties were determined using nonlinear mixed-effects modelling.
- Artesunate is rapidly hydrolysed in vivo to DHA, contributing to its antimalarial activity.
Takeaway
This study looked at how well a malaria treatment called artesunate works when given as a rectal suppository, finding that most patients absorb it well.
Methodology
The study involved two Phase II and three Phase III studies with blood samples taken from patients to measure drug concentrations and build a pharmacokinetic model.
Potential Biases
Potential biases may arise from the open-label design and the variability in drug absorption among patients.
Limitations
The study had to make several modeling assumptions due to large intra- and inter-individual variability in drug concentrations.
Participant Demographics
Patients included adults and children from Africa and Southeast Asia with moderately severe malaria.
Statistical Information
P-Value
p<0.05
Confidence Interval
95% CI: 0.36–1.92
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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