8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models

M. S. Bartlett, S. F. Queener, R. R. Tidwell, W. K. Milhous, J. D. Berman, W. Y. Ellis, J. W. Smith

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Abstract

Three 8-aminoquinolines from the Walter Reed Army Institute for Research (WRAIR), WR6026, WR238605, and WR242511, strongly inhibited Pneumocystis carinii growth in vitro at 1 μg/ml. This activity was similar to that of primaquine. In rat therapy models, the WRAIR compounds affected Pneumocystis pneumonia at doses as low as 0.25 mg/kg (WR242511) or 0.5 mg/kg (WR6026 and WR238605). At these doses, primaquine alone was ineffective as therapy. In a rat prophylaxis model, all three WRAIR 8-aminoquinolines were extremely effective at daily doses of 0.57 mg/kg, showing activity greater than that of primaquine at this dosage and comparable to that of trimethoprim-sulfamethoxazole at 50/250 mg/kg.

Original languageEnglish (US)
Pages (from-to)277-282
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume35
Issue number2
DOIs
StatePublished - Jan 1 1991

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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