Publication: Effects of α-thalassemia on pharmacokinetics of the antimalarial agent artesunate
Issued Date
1998-09-01
Resource Type
ISSN
00664804
Other identifier(s)
2-s2.0-0031679937
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.42, No.9 (1998), 2332-2335
Suggested Citation
Wanida Ittarat, Sornchai Looareesuwan, Pensri Pootrakul, Petchmanee Sumpunsirikul, Phantip Vattanavibool, Steven R. Meshnick Effects of α-thalassemia on pharmacokinetics of the antimalarial agent artesunate. Antimicrobial Agents and Chemotherapy. Vol.42, No.9 (1998), 2332-2335. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/18495
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Effects of α-thalassemia on pharmacokinetics of the antimalarial agent artesunate
Abstract
Thalassemia is common in Southeast Asia, where artemisinin derivatives are frequently used in the treatment of malaria. It has been previously reported that artemisinin derivatives can be concentrated by uninfected thalassemic erythrocytes in vitro but not by normal erythrocytes. As a follow-up to this report, we studied the antimalarial kinetics of intravascular artesunate (2.4 mg/kg of body weight) in 10 persons with normal hemoglobins and in 10 patients with thalassemia (2 with α-thalassemia type 1-hemoglobin Constant Spring and 8 with α-thalassemia type 1-α-thalassemia type 2). Concentrations of artesunate and its active metabolites in plasma were measured by bioassay and expressed relative to those of dihydroartemisinin, the major biologically active metabolite. Concentrations of intravascular artesunate in plasma peaked in both the normal individuals and the thalassemic individuals 15 min after injection (the first time point). Plasma drug concentrations at all time intervals, except that at 1 h, were significantly higher in thalassemic subjects than in normal subjects (P < 0.05). The area under the concentration-time curve was 9-fold higher (P < 0.001) and the volume of distribution at steady state was 15-fold lower (P < 0.001) in thalassemic than in normal subjects. In light of the potential neurotoxicity of artemisinin derivatives, these results suggest that thalassemic subjects may need a drug administration regimen different from that of normal patients.