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Antimicrob Agents Chemother. 1995 September; 39(9): 2023–2026.
PMCID: PMC162875

Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.


The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO.

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Selected References

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  • Angel MF, Narayanan K, Swartz WM, Ramasastry SS, Kuhns DB, Basford RE, Futrell JW. Deferoxamine increases skin flap survival: additional evidence of free radical involvement in ischaemic flap surgery. Br J Plast Surg. 1986 Oct;39(4):469–472. [PubMed]
  • Bowern N, Ramshaw IA, Badenoch-Jones P, Doherty PC. Effect of an iron-chelating agent on lymphocyte proliferation. Aust J Exp Biol Med Sci. 1984 Dec;62(Pt 6):743–754. [PubMed]
  • Bradley B, Prowse SJ, Bauling P, Lafferty KJ. Desferrioxamine treatment prevents chronic islet allograft damage. Diabetes. 1986 May;35(5):550–555. [PubMed]
  • Clarkson AB, Jr, Sarić M, Grady RW. Deferoxamine and eflornithine (DL-alpha-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1990 Sep;34(9):1833–1835. [PMC free article] [PubMed]
  • Davey RT, Jr, Masur H. Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother. 1990 Apr;34(4):499–504. [PMC free article] [PubMed]
  • Fudman EJ, Till GO, Fox IH. Deferoxamine induced decreases of lipid peroxides in rheumatoid arthritis. J Rheumatol. 1987 Aug;14(4):686–691. [PubMed]
  • Gordeuk VR, Thuma PE, Brittenham GM. Iron chelation therapy for malaria. Adv Exp Med Biol. 1994;356:371–383. [PubMed]
  • Hershko C. Biological models for studying iron chelating drugs. Baillieres Clin Haematol. 1989 Apr;2(2):293–321. [PubMed]
  • Hershko C, Pinson A, Link G. Iron chelation. Blood Rev. 1990 Mar;4(1):1–8. [PubMed]
  • Kovacs JA, Hiemenz JW, Macher AM, Stover D, Murray HW, Shelhamer J, Lane HC, Urmacher C, Honig C, Longo DL, et al. 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. [PubMed]
  • Kruck TP, Teichert-Kuliszewska K, Fisher E, Kalow W, McLachlan DR. High-performance liquid chromatographic analysis of desferrioxamine. Pharmacokinetic and metabolic studies. J Chromatogr. 1988 Dec 9;433:207–216. [PubMed]
  • Lee P, Mohammed N, Marshall L, Abeysinghe RD, Hider RC, Porter JB, Singh S. Intravenous infusion pharmacokinetics of desferrioxamine in thalassaemic patients. Drug Metab Dispos. 1993 Jul-Aug;21(4):640–644. [PubMed]
  • Merali S, Chin K, Grady RW, Weissberger L, Clarkson AB., Jr Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine. Antimicrob Agents Chemother. 1995 Jul;39(7):1442–1444. [PMC free article] [PubMed]
  • Meyer-Brunot HG, Keberle H. The metabolism of desferrioxamine B and ferrioxamine B. Biochem Pharmacol. 1967 Mar;16(3):527–535. [PubMed]
  • Peto TE, Thompson JL. A reappraisal of the effects of iron and desferrioxamine on the growth of Plasmodium falciparum 'in vitro': the unimportance of serum iron. Br J Haematol. 1986 Jun;63(2):273–280. [PubMed]
  • Polson RJ, Jawed A, Bomford A, Berry H, Williams R. Treatment of rheumatoid arthritis with desferrioxamine: relation between stores of iron before treatment and side effects. Br Med J (Clin Res Ed) 1985 Aug 17;291(6493):448–448. [PMC free article] [PubMed]
  • Singh S, Mohammed N, Ackerman R, Porter JB, Hider RC. Quantification of desferrioxamine and its iron chelating metabolites by high-performance liquid chromatography and simultaneous ultraviolet-visible/radioactive detection. Anal Biochem. 1992 May 15;203(1):116–120. [PubMed]
  • Summers MR, 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. [PubMed]
  • Weinberg GA. Iron chelators as therapeutic agents against Pneumocystis carinii. Antimicrob Agents Chemother. 1994 May;38(5):997–1003. [PMC free article] [PubMed]
  • Weinberg GA, Shaw MM. Suppressive effect of deferoxamine on the growth of Pneumocystis carinii in vitro. J Protozool. 1991 Nov-Dec;38(6):223S–224S. [PubMed]

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