THE DISPOSITION OF INTRAMUSCULAR ARTEMETHER IN CHILDREN WITH CEREBRALMALARIA - A PRELIMINARY-STUDY

The disposition of intramuscular artemether (AM) was studied in 26 Ken yan children with cerebral malaria. Antimalarial activity determined b y bioassay was compared with total plasma AM plus dihydroartemisinin ( DHA) determined by high power liquid chromatography (HPLC). Therapeuti c levels were achieved in most subjects (21/26) within 1 h of receivin g intramuscular AM (3.2 mg/kg), with close correlation between bioassa y and HPLC measurements (r = 0.706). However, there was marked inter-i ndividual variation, antimalarial activity was undetectable in 5 subje cts ('non-absorbers'), and plasma concentrations were lower in subject s with respiratory distress. The 50% parasite clearance time was signi ficantly longer in non-absorbers (mean = 13.1 h, SD = 10.8 vs. mean = 7.8 h, SD = 5.5; P = 0.013). We conclude that the bioavailability of i ntramuscular AM in children with severe malaria may be highly variable , particularly in the presence of respiratory distress, and may be ass ociated with an inadequate therapeutic response.