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