title: Proguanil plus sulfamethoxazole is not causally prophylactic in the Macaca mulatta--Plasmodium cynomolgi model.
abstract: New drugs for causal prophylaxis of malaria are needed. A proguanil/sulfamethoxazole combination was investigated using a rhesus monkey model (Macaca mulatta infected with Plasmodium cynomolgi) to determine whether causal prophylaxis could be achieved. When a five-day regimen of proguanil (40 mg/kg/day) combined with sulfamethoxazole (100 mg/kg/day) was used, infection of all animals (6 of 6) was observed, with an extended prepatent period (median 40 days). Two control animals became infected on days 9 and 23 following sporozoite inoculation. Plasma concentrations indicated that proguanil and sulfamethoxazole were adequately absorbed and metabolized to cycloguanil and N4-acetylsulfamethoxazole, respectively. Analysis of liver biopsy specimens demonstrated that the drugs were present two days following sporozoite inoculation but were not detectable one week later. Proguanil plus sulfamethoxazole does not eliminate exoerythrocytic-stage parasites in the rhesus monkey--P. cynomolgi model.
authors.affiliation: Department of Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: G D
authors.initials: GD
authors.lastname: Shanks
authors.forename: M D
authors.initials: MD
authors.lastname: Edstein
authors.forename: A L
authors.initials: AL
authors.lastname: Chedester
authors.forename: C D
authors.initials: CD
authors.lastname: Smith
authors.forename: K D
authors.initials: KD
authors.lastname: Corcoran
authors.forename: M
authors.initials: M
authors.lastname: Ngampochjana
authors.forename: P
authors.initials: P
authors.lastname: Hansukjariya
authors.forename: J
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: H K
authors.initials: HK
authors.lastname: Webster
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D008099:Liver / Q000378:metabolism; D008253:Macaca mulatta; D008288:Malaria / Q000517:prevention & control*; D008297:Male; D016789:Plasmodium cynomolgi; D002727:Proguanil / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013420:Sulfamethoxazole / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D013420:Sulfamethoxazole; D002727:Proguanil