Conclusions
Methaemoglobinaemia is associated with exposure to therapeutic doses of
8-aminoquinoline drugs. The proportion of methaemoglobin to haemoglobin
correlates with the efficacy of anti-relapse therapy, but methaemoglobin
appears to be uninvolved directly either in that activity or in
haemolytic toxicity in G6PD-deficient patients. This suggests that the
oxidative processes which result in methaemoglobinaemia are necessary,
but they are not sufficient, for the radical curative activity of the
8-aminoquinoline antimalarial drugs. Although there is substantial
inter-individual variation in iatrogenic methaemoglobinaemia, the
overall clinical data suggest that methaemoglobinaemia is a
pharmacodynamic correlate of radical curative activity. Measurement of
methaemoglobinaemia might be useful in drug screening and dose
evaluation.
Acknowledgements: We are very grateful to our many colleagues
who have contributed extensively to the clinical studies.
Declaration of Interests. We have no conflicts of interest.
Ethics approval and consent to participate. Not relevant.
Availability of data and material : All data used are available
from the original publications.
Funding : Wellcome Trust