The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria

• Published in: European journal of clinical pharmacology Vol. 62; no. 12; pp. 1003 - 1009
• Main Authors: NEWTON, Paul N, BARNES, Karen I, SMITH, Peter J, EVANS, Alicia C, CHIERAKUL, Wirongrong, RUANGVEERAYUTH, Ronatrai, WHITE, Nicholas J
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.12.2006; Berlin Springer Nature B.V
• Subjects: Administration, Oral; Adolescent; Adult; Adults; Age Factors; Antimalarials - administration & dosage; Antimalarials - pharmacokinetics; Antimalarials - therapeutic use; Area Under Curve; Artemisinins - administration & dosage; Artemisinins - metabolism; Artemisinins - pharmacokinetics; Artemisinins - therapeutic use; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Dose-Response Relationship, Drug; Drug dosages; Drug Therapy, Combination; Electrochemistry - methods; Female; Half-Life; Human protozoal diseases; Humans; Infectious diseases; Injections, Intravenous; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - pathology; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Parasitic diseases; Pharmacology; Pharmacology. Drug treatments; Pilot Projects; Protozoal diseases; Quinine - pharmacokinetics; Quinine - therapeutic use; Sesquiterpenes - administration & dosage; Sesquiterpenes - metabolism; Sesquiterpenes - pharmacokinetics; Sesquiterpenes - therapeutic use; Severity of Illness Index; Thailand; Thailand; Human; Protozoa; Antimalarial; Apicomplexa; Protozoal disease; Intravenous administration; Malaria; Severe malaria; Parasitosis; Infection; Antiprotozoal agent; Plasmodium falciparum; Artesunate; Adult; Parasiticide; Pharmacokinetics
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-006-0203-2

Intravenous artesunate is commonly used in the emergency treatment of patients with severe falciparum malaria in Asia. The choice of doses used has been empirical. To inform dosage recommendations we assessed the pharmacokinetics of intravenous artesunate after the first dose. As part of a clinical trial of artesunate in adults with severe falciparum malaria in western Thailand, we assayed plasma concentrations of artesunate and the principal biologically active metabolite dihydroartemisinin (DHA) in 17 patients given an initial dose of 2.4 mg/kg body weight of intravenous artesunate. Drug levels were measured using high performance liquid chromatography with mass spectroscopy-electrospray ionisation detection. Median (range) observed DHA Cmax was 2128 (513-5789) nmol/L, elimination half-life was 0.34 (0.14-0.87) h, and the time to the last detectable DHA was 2 h. The large inter-individual variability (10 fold) in DHA Cmax and AUC in patients with potentially lethal, severe malaria, suggests that 2.4 mg/kg should be the minimum daily dose in severe malaria.