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. 1995 Jul;39(7):1442–1444. doi: 10.1128/aac.39.7.1442

Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine.

S Merali 1, K Chin 1, R W Grady 1, L Weissberger 1, A B Clarkson Jr 1
PMCID: PMC162759  PMID: 7492082

Abstract

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.

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Selected References

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  1. Allain P., Chaleil D., Mauras Y., Beaudeau G., Varin M. C., Poignet J. L., Ciancioni C., Ang K. S., Cam G., Simon P. Pharmacokinetics of desferrioxamine and of its iron and aluminium chelates in patients on haemodialysis. Clin Chim Acta. 1987 Dec;170(2-3):331–338. doi: 10.1016/0009-8981(87)90144-6. [DOI] [PubMed] [Google Scholar]
  2. Allain P., Mauras Y., Chaleil D., Simon P., Ang K. S., Cam G., Le Mignon L., Simon M. Pharmacokinetics and renal elimination of desferrioxamine and ferrioxamine in healthy subjects and patients with haemochromatosis. Br J Clin Pharmacol. 1987 Aug;24(2):207–212. doi: 10.1111/j.1365-2125.1987.tb03163.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang T. M., Barre P. Effect of desferrioxamine on removal of aluminum and iron by coated charcoal haemoperfusion and haemodialysis. Lancet. 1983 Nov 5;2(8358):1051–1053. doi: 10.1016/s0140-6736(83)91039-5. [DOI] [PubMed] [Google Scholar]
  4. Clarkson A. B., Jr, Sarić M., Grady R. W. Deferoxamine and eflornithine (DL-alpha-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1990 Sep;34(9):1833–1835. doi: 10.1128/aac.34.9.1833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davey R. T., Jr, Masur H. Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1990 Apr;34(4):499–504. doi: 10.1128/aac.34.4.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gordeuk V. R., Thuma P. E., Brittenham G. M. Iron chelation therapy for malaria. Adv Exp Med Biol. 1994;356:371–383. doi: 10.1007/978-1-4615-2554-7_39. [DOI] [PubMed] [Google Scholar]
  7. Gosey L. L., Howard R. M., Witebsky F. G., Ognibene F. P., Wu T. C., Gill V. J., MacLowry J. D. Advantages of a modified toluidine blue O stain and bronchoalveolar lavage for the diagnosis of Pneumocystis carinii pneumonia. J Clin Microbiol. 1985 Nov;22(5):803–807. doi: 10.1128/jcm.22.5.803-807.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kovacs J. A., Hiemenz J. W., Macher A. M., Stover D., Murray H. W., Shelhamer J., Lane H. C., Urmacher C., Honig C., Longo D. L. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med. 1984 May;100(5):663–671. doi: 10.7326/0003-4819-100-5-663. [DOI] [PubMed] [Google Scholar]
  9. Lee P., Mohammed N., Marshall L., Abeysinghe R. D., Hider R. C., Porter J. B., Singh S. Intravenous infusion pharmacokinetics of desferrioxamine in thalassaemic patients. Drug Metab Dispos. 1993 Jul-Aug;21(4):640–644. [PubMed] [Google Scholar]
  10. Meyer-Brunot H. G., Keberle H. The metabolism of desferrioxamine B and ferrioxamine B. Biochem Pharmacol. 1967 Mar;16(3):527–535. doi: 10.1016/0006-2952(67)90100-1. [DOI] [PubMed] [Google Scholar]
  11. Pippard M. J., Letsky E. A., Callender S. T., Weatherall D. J. Prevention of iron loading in transfusion-dependent thalassaemia. Lancet. 1978 Jun 3;1(8075):1178–1181. doi: 10.1016/s0140-6736(78)90968-6. [DOI] [PubMed] [Google Scholar]
  12. Pollack S., Rossan R. N., Davidson D. E., Escajadillo A. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys. Proc Soc Exp Biol Med. 1987 Feb;184(2):162–164. doi: 10.3181/00379727-184-42461. [DOI] [PubMed] [Google Scholar]
  13. Sarić M., Clarkson A. B., Jr Ornithine decarboxylase in Pneumocystis carinii and implications for therapy. Antimicrob Agents Chemother. 1994 Nov;38(11):2545–2552. doi: 10.1128/aac.38.11.2545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Summers M. R., Jacobs A., Tudway D., Perera P., Ricketts C. Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects. Br J Haematol. 1979 Aug;42(4):547–555. doi: 10.1111/j.1365-2141.1979.tb01167.x. [DOI] [PubMed] [Google Scholar]
  15. Weinberg G. A. Iron chelators as therapeutic agents against Pneumocystis carinii. Antimicrob Agents Chemother. 1994 May;38(5):997–1003. doi: 10.1128/aac.38.5.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Weinberg G. A., Shaw M. M. Suppressive effect of deferoxamine on the growth of Pneumocystis carinii in vitro. J Protozool. 1991 Nov-Dec;38(6):223S–224S. [PubMed] [Google Scholar]
  17. Yinnon A. M., Theanacho E. N., Grady R. W., Spira D. T., Hershko C. Antimalarial effect of HBED and other phenolic and catecholic iron chelators. Blood. 1989 Nov 1;74(6):2166–2171. [PubMed] [Google Scholar]

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