Proguanil plus sulfamethoxazole is not causally prophylactic in the Macaca mulatta--Plasmodium cynomolgi model.
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.
Shanks
G D
GD
Department of Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Edstein
M D
MD
Chedester
A L
AL
Smith
C D
CD
Corcoran
K D
KD
Ngampochjana
M
M
Hansukjariya
P
P
Sattabongkot
J
J
Webster
H K
HK
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*
D004338:Drug Combinations; D013420:Sulfamethoxazole; D002727:Proguanil