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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effects of alpha-thalassemia on pharmacokinetics of the antimalarial agent artesunate.

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 alpha-thalassemia type 1-hemoglobin Constant Spring and 8 with alpha-thalassemia type 1-alpha-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.[1]

References

  1. Effects of alpha-thalassemia on pharmacokinetics of the antimalarial agent artesunate. Ittarat, W., Looareesuwan, S., Pootrakul, P., Sumpunsirikul, P., Vattanavibool, P., Meshnick, S.R. Antimicrob. Agents Chemother. (1998) [Pubmed]
 
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