Evidence based optimal dosing of intravenous artesunate in children with severe falciparum malaria

In this study, we performed population pharmacokinetic modeling of plasma concentration data from 80 children with severe falciparum malaria in the Democratic Republic of Congo who were given 2.4 mg/kg of artesunate intravenously. Bayesian hierarchical modeling and a two-compartment parent drug-metabolite pharmacokinetic model for artesunate were used to describe the population pharmacokinetics of artesunate and its main biologically active metabolite dihydroartemisinin. We then generated a virtual population representative of the target population in which the drug is used and simulated the total first-dose exposures. Our study shows that the majority of younger children given the lower 2.4 mg/kg dose of intravenous artesunate do not reach the same drug exposures as older children above 20 kg. This finding supports withdrawal of the FDA's recent lower artesunate dose recommendation as parenteral artesunate is an extremely safe and well-tolerated drug and there is potential for harm from underdosing in this rapidly lethal infection.PMID:37666798 | DOI:10.1002/cpt.3041
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Source Type: research