Efficacy of Intermittent Dosage of 8-Aminoquinolines for Therapy orProphylaxis of Pneumocystis Pneumonia in Rats

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Abstract
Experimental 8-aminoquinolines from Walter Reed Army Institute for Research are effective for prophylaxis or therapy of Pneumocystis carinii pneumonia in rat models. In the present study, primaquine, WR6026, and WR238605 were tested in prophylaxis and treatment models of P. carinii pneumonia to compare the effectiveness of continuous versus intermittent dosing. For treatment of P. carinii pneumonia, the drugs showed detectable effects when given once every 4 days (primaquine and WR6026 at doses >8 mg/kg; WR238605 at doses >2 mg/kg), For prophylaxis, WR6026 and WR238605 were effective given alone daily (WR6026 at doses >0.25 mg/kg; WR238605 at doses >0.57 mg/kg). WR6026 and WR238605 at 4 mg/kg given once every 4 days for prophylaxis were as effective as daily trimethoprim-sulfamethoxazole. These studies suggest that higher doses of 8-aminoquinolines administered at appropriate intervals may be as effective as continuous dosing for prophylaxis of P. carinii pneumonia.

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