THE DISPOSITION OF ORAL AND INTRAMUSCULAR PYRIMETHAMINE SULFADOXINE IN KENYAN CHILDREN WITH HIGH PARASITEMIA BUT CLINICALLY NON-SEVERE FALCIPARUM-MALARIA

1 H.p.l.c. methods are described for the measurement of pyrimethamine and sulphadoxine in small volumes of plasma dried on filter paper strips. 2 Pyrimethamine/sulphadoxine (Fansidar, Hoffman LaRoche) was given by mouth and by intramuscular injection to children with uncomplicated falciparum malaria but with high parasitaemia (n = 8 for both routes; pyrimethamine 1.25 mg kg-1, sulphadoxine 25 mg kg-1). 3 Plasma concentrations of pyrimethamine and sulphadoxine associated with synergistic effects against pyrimethamine-resistant strains of Plasmodium falciparum in vitro were achieved within 1 h of administration and were maintained beyond the end of sampling. 4 After both oral and parenteral administration the plasma concentrations of both compounds were lower than those predicted by data from healthy subjects. 5 Areas under the plasma concentration-time curves of sulphadoxine after oral and i.m. administration did not differ significantly, although maximum plasma drug concentrations were higher after the i.m. route (P = 0.03). 6 The AUC values of pyrimethamine did not differ significantly between the two routes of administration. However, after i.m. administration AUC(0,24 h) values were smaller (P = 0.03), and the time to maximum plasma drug concentration (t(max)) was longer (P = 0.004) than when the drug was given orally.