ANTIPNEUMOCYSTIS ACTIVITY OF 17C91, A PRODRUG OF ATOVAQUONE

The prophylactic efficacy of 17C91, a carbamate prodrug of atovaquone (ATQ), was investigated in a severe combined immunodeficient mouse mod el of Pneumocystis carinii pneumonia (PCP). At an oral dosage equivale nt to 100 mg of ATQ per kg of body weight per day, 17C91 protected 9 o f 10 mice from PCP and had a prophylactic efficacy comparable to that of co-trimoxazole (at 250 mg of sulfamethoxazole plus 50 mg of trimeth oprim per kg per day orally). The intensity of P. carinii infection (i nfection score) of mice treated vith 17C91 correlated with the concent ration of ATQ in the plasma, with clearance of the infection associate d with plasma ATQ levels of >35 mu g/ml. 17C91 given orally provided e nhanced levels of ATQ in the plasma compared with the conventional ATQ formulation. Additional studies reported in this paper demonstrate th at the prophylactic activity of 17C91 against PCP in severe combined i mmunodeficient mice is comparable to that of a new oral microparticula te formulation of ATQ.