Efficacy and pharmacokinetics of atovaquone and proguanil in children with multidrug-resistant Plasmodium falciparum malaria

摘要: Abstract A trial was conducted in 32 Thai children with uncomplicated multidrug-resistant falciparum malaria to assess the efficacy, safety and pharmacokinetics of atovaquone proguanil; plasma concentrations atovaquone, proguanil its metabolite, cycloguanil, were measured a subset 9 children. The received (17 mg/kg/d for 3 d) plus (7 d). Twenty-six who had only Plasmodium infection remained hospital 28 d assessed drug efficacy. combination regimen produced cure rate 100%. Parasite fever clearance times 47 h (range 8–75) 50 7–111), respectively. Atovaquone rapidly absorbed, median time peak 6 6–24) 6–12), Peak cycloguanil achieved between 12 (median 6) after administration proguanil. Mean concentration on day 5·1 μg/mL (SD = 2·1). mean 306 ng/mL 108) compared 44·3 27.3) cycloguanil. values AUC (area under concentration-time curve) 161·8 · 126·9) 4646 1226) proguanil, 787 397) Terminal elimination half-lives estimated as 31·8 8.9), 14·9 3·3) 14·6 2·6), No major adverse effect attributable study drugs. Atovaquone/proguanil is safe highly effective, should be especially valuable treatment malaria.