Safety and pharmacokinetic properties of a new formulation of parenteral artesunate in healthy Thai volunteers
Issued Date
2024-10-03
Resource Type
eISSN
14752875
Scopus ID
2-s2.0-85205605370
Pubmed ID
39363296
Journal Title
Malaria journal
Volume
23
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Malaria journal Vol.23 No.1 (2024) , 296
Suggested Citation
Tarning J., Hanboonkunupakarn B., Hoglund R.M., Chotivanich K., Mukaka M., Pukrittayakamee S., Day N.P.J., White N.J., Dondorp A.M., Jittamala P. Safety and pharmacokinetic properties of a new formulation of parenteral artesunate in healthy Thai volunteers. Malaria journal Vol.23 No.1 (2024) , 296. doi:10.1186/s12936-024-05085-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101594
Title
Safety and pharmacokinetic properties of a new formulation of parenteral artesunate in healthy Thai volunteers
Corresponding Author(s)
Other Contributor(s)
Abstract
BACKGROUND: Parenteral artesunate is the first-line therapy for severe malaria. Artesunate, in its current formulation, must be prepared immediately before administration by first dissolving in sodium bicarbonate solution and then diluting in saline. A novel solvent for rapid and stable single step reconstitution of artesunate was recently developed showing improved solubility and stability. This study aimed to compare the safety and pharmacokinetic properties of the currently available and newly developed parenteral formulation of artesunate in healthy Thai volunteers. METHODS: This was an open-label, randomized, 4 periods, 4-treatments, 24-sequence, single-dose, cross-over study in 72 male and female healthy Thai volunteers. Frequent pharmacokinetic samples were collected in all volunteers at each dose occasion. Observed concentration-time profiles were analysed with a non-compartmental approach followed by a bioequivalence evaluation. RESULTS: Both intramuscular and intravenous administrations of the new parenteral formulation of artesunate were safe and well-tolerated, with no additional safety signals compared to the currently used formulation. The pharmacokinetic properties of artesunate and its active metabolite, dihydroartemisinin, were well-characterized, and showed rapid conversion of artesunate into dihydroartemisinin. Intramuscular administration of the newly formulated artesunate resulted in almost complete bioavailability of dihydroartemisinin. The pharmacokinetic properties were similar between the old and new formulation. CONCLUSIONS: The new and more easily prepared formulation of artesunate was safe and well-tolerated, with similar pharmacokinetic properties compared to the currently used formulation. Dihydroartemisinin, the active metabolite responsible for the majority of the anti-malarial effect, showed equivalent exposure after both intravenous and intramuscular administration of artesunate, suggesting that both routes of administration should generate comparable therapeutic effects. TRIAL REGISTRATION: The study was registered to clinicaltrials.gov (#TCTR20170907002).