Activity of minocycline against Toxoplasma gondii infection in mice.
The chemotherapeutic activity of minocycline, a semi-synthetic tetracycline analogue, was evaluated in a murine model of toxoplasmosis. A lethal acute toxoplasmosis was produced by injecting 10(5) tachyzoites of the RH strain of Toxoplasma gondii into the peritoneal cavities of Swiss-Webster mice. When infected mice were treated once daily for 12 days, starting 2 h after challenge, the survival and cure rates were 100% and 40% respectively after minocycline alone (100 mg/kg per day), 0% and 0% after pyrimethamine alone (8.5 mg/kg per day), and 100% and 50% after combination of the two drugs at the same dosages. Absolute survival and cure with minocycline were observed when mice were treated with two daily doses of 100 mg/kg for 12 days. Mice chronically infected with a low virulent strain of T. gondii (Me49) showed a significant reduction in the number of brain cysts after three weeks of treatment with 50 mg/kg per day of minocycline. Minocycline serum levels after a single oral administration of 50 mg/kg or 100 mg/kg to normal mice, peaked at 1.8 mg/l and 10 mg/l after 1 h, respectively, and showed an extended half-life.
Chang
H R
HR
Department of Microbiology, University of Geneva Medical School, Switzerland.
Comte
R
R
Piguet
P F
PF
Pechère
J C
JC
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004353:Drug Evaluation, Preclinical; D005260:Female; D051379:Mice; D008911:Minocycline / Q000097:blood / Q000627:therapeutic use*; D011739:Pyrimethamine / Q000627:therapeutic use; D012074:Remission Induction; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000469:parasitology
D008911:Minocycline; D011739:Pyrimethamine