Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pneumocystis carinii pneumonia is often the terminal event for patients with the acquired immunodeficiency syndrome. Eflornithine (DL-alpha-difluoromethylornithine [DFMO]; Ornidyl; Merrell Dow Research Institute, Cincinnati, Ohio) has been used successfully against this protozoan disease in limited clinical trials, although not all patients respond to therapy. In contrast, results of the only reported experiments with DFMO in an animal model were negative. We retested DFMO against P. carinii in an immunosuppressed rat model by inclusion of 3% DFMO in the drinking water, a dose rate about twice that used previously. A combination of trimethoprim and sulfamethoxazole, a proven anti-P. carinii agent, was used as a positive control. After 3 weeks of anti-P. carinii pneumonia therapy, the surviving rats were sacrificed and the degree of parasitosis was judged by examination of lung sections stained with silver methenamine to reveal cysts. In three separate experiments, DFMO showed definite anti-P. carinii pneumonia activity; the parasitosis of DFMO-treated animals was significantly less than that of control animals (P less than 0.001 for all experiments). DFMO was not as active as trimethoprim-sulfamethoxazole, however. Several other experimental therapies were tested, including dapsone and two additional antiprotozoal agents: suramin and diminazene aceturate (Berenil; Farbwerke Hoechst, Frankfurt, Federal Republic of Germany). Diminazene aceturate, a veterinary drug related to the standard anti-P. carinii pneumonia agent pentamidine, was very active (P less than 10(-10]. Suramin and dapsone were weakly active. The combinations suramin-diminazene aceturate and suramin-DFMO were tested, but they were antagonistic rather than synergistic.
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PMID:Efficacy of DL-alpha-difluoromethylornithine in a rat model of Pneumocystis carinii pneumonia. 314 46

The rapid depletion of Pneumocystis carinii polyamines caused by in vitro exposure to DL-alpha-difluoromethylornithine (DFMO; also called eflornithine or Ornidyl) and the rapid repletion following removal of this drug suggested that the in vivo efficacy of DFMO against P. carinii pneumonia (PCP) may be limited by troughs in drug concentration resulting from the schedule of administration. This led to the prediction that, compared with the response to the standard animal protocol of administering DFMO in drinking water, the response of a rat model of PCP to DFMO would be lessened by bolus administration and improved by continuous infusion. These predictions were confirmed. Intraperitoneal bolus administration of up to 3 g of DFMO kg of body weight-1 was completely ineffective, although this dose has been shown to be effective when given in the drinking water. Conversely, continuous infusion improved the response against PCP seven- to ninefold over the response to drinking water administration. These findings suggest that, compared with the standard clinical investigational protocol for treatment of PCP with DFMO given in four divided daily doses, continuous infusion combined with monitoring of drug concentrations in plasma may improve efficacy and/or reduce the already low rate of adverse effects.
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PMID:Continuous infusion of DL-alpha-difluoromethylornithine and improved efficacy against a rat model of Pneumocystis carinii pneumonia. 889 Nov 37