Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine.
The iron-chelating drug deferoxamine mesylate (DFO) is active against Pneumocystis carinii in vitro and in rat and mouse models of P. carinii pneumonia. Because DFO has a short half-life, daily divided or continuous dosage was expected to improve the dose response, as is the case with DFO treatment of malaria. Therefore, results of single daily intraperitoneal injections were compared with results of an evenly divided four-times-daily dosage and the efficacy of delivery with implanted infusion pumps. The highest bolus dosage (1,000 mg kg-1 of body weight day-1) was as effective as the standard combination of trimethoprim with sulfamethoxazole. Unexpectedly, very little improvement was observed with the divided or continuous dosage, and several mechanisms that could account for this are discussed.
D000818:Animals; D003676:Deferoxamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006207:Half-Life; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003676:Deferoxamine