title: Efficacy of a novel sublingual spray formulation of artemether in African children with Plasmodium falciparum malaria.
abstract: The efficacy of sublingual artemether (ArTiMist) was investigated in two studies. In study 1, 31 children were randomized to sublingual artemether (n = 16) or intravenous (i.v.) quinine (n = 15). In study 2, 151 children were randomized to sublingual artemether (n = 77) or i.v. quinine (n = 74). For both studies, patients weighed between 5 and 15 kg and had either severe or complicated malaria based on WHO criteria, or they had uncomplicated malaria but were unable to tolerate oral medication as a result of nausea, vomiting, or diarrhea. Patients received either 3 mg/kg of body weight of sublingual artemether or a loading dose of 20 mg/kg of i.v. quinine followed by 10 mg/kg every 8 h i.v. thereafter. The primary endpoint was parasitological success, defined as a reduction in parasite count of ≥90% of that at baseline at 24 h after the first dose. Other endpoints based on parasite clearance and clinical response were evaluated. In study 1, there were parasitological success rates of 93.3% (14/15) and 66.7% (10/15) for the sublingual artemether and quinine treatments, respectively. In study 2, 94.3% (66/70) of the ArTiMist-treated patients and 39.4% (28/71) of the quinine-treated patients had parasitological success (P < 0.0001). Indicators of parasite clearance (parasite clearance time [PCT], time for parasite count to fall by 50% [PCT50], time for parasite count to fall by 90% [PCT90], and percent reduction in parasitemia from baseline at 24 h [PRR24]) were significantly superior for children treated with sublingual artemether compared to those treated with i.v. quinine. There were no differences between treatments for the clinical endpoints, such as fever clearance time. The local tolerability of sublingual artemether was good. Sublingual artemether leads to rapid parasite clearance and clinical recovery. (Studies 1 and 2 are registered at ClinicalTrials.gov under registration numbers NCT01047436 and NCT01258049, respectively.).
authors: Xidea Solutions Limited, Watford, Hertfordshire, England daryl@xideasolutions.com.
authors: Daryl
authors: D
authors: Bendel
authors: Kigali University Teaching Hospital and University of Rwanda, College of Medicine & Health Sciences, Kigali, Rwanda.
authors: Stephen
authors: S
authors: Rulisa
authors: Navrongo Health Research Centre, Kasenna-Nankana District, Upper East Region, Ghana.
authors: Patrick
authors: P
authors: Ansah
authors: Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso.
authors: Sodiomon
authors: S
authors: Sirima
mesh_terms: D000286:Administration, Sublingual; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077549:Artemether