Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans

Philip E Thuma, Nancy F. Olivieri, George F. Mabeza, Godfrey Biemba, Dean Parry, Stenford Zulu, Frank F. Fassos, Robert A. Mcclelland, Gideon Koren, Gary M. Brittenham, Victor R. Gordeuk

Research output: Contribution to journalArticle

Abstract

While the parenteral iron-chelating agent desferrioxamine B has anti- malarial activity in humans, the usefulness of an orally active chelator for this indication has not been investigated previously in vivo. We conducted a prospective, double-blind, placebo-controlled, cross-over trial of deferiprone (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight, dosages that are effective for treating iron overload. No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment. The mean peak plasma concentration of deferiprone (108.9 ± 24.9 μmol/L) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro, but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo. No evidence of deferiprone- associated hematological toxicity was noted in this short-term study of these subjects, all of whom had clinical evidence of normal body iron stores. Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator, additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified. In contrast, further efforts are needed to develop other orally active iron-chelating agents specifically for their antimalarial action.

Original languageEnglish (US)
Pages (from-to)358-364
Number of pages7
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume58
Issue number3
StatePublished - 1998
Externally publishedYes

Fingerprint

Parasitemia
Plasmodium falciparum
Chelating Agents
Iron
Antimalarials
Iron Chelating Agents
Deferoxamine
Iron Overload
deferiprone
Growth
Neutropenia
Human Activities
Cross-Over Studies
Parasites
Placebos
Body Weight

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans. / Thuma, Philip E; Olivieri, Nancy F.; Mabeza, George F.; Biemba, Godfrey; Parry, Dean; Zulu, Stenford; Fassos, Frank F.; Mcclelland, Robert A.; Koren, Gideon; Brittenham, Gary M.; Gordeuk, Victor R.

In: American Journal of Tropical Medicine and Hygiene, Vol. 58, No. 3, 1998, p. 358-364.

Research output: Contribution to journalArticle

Thuma, PE, Olivieri, NF, Mabeza, GF, Biemba, G, Parry, D, Zulu, S, Fassos, FF, Mcclelland, RA, Koren, G, Brittenham, GM & Gordeuk, VR 1998, 'Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans', American Journal of Tropical Medicine and Hygiene, vol. 58, no. 3, pp. 358-364.
Thuma, Philip E ; Olivieri, Nancy F. ; Mabeza, George F. ; Biemba, Godfrey ; Parry, Dean ; Zulu, Stenford ; Fassos, Frank F. ; Mcclelland, Robert A. ; Koren, Gideon ; Brittenham, Gary M. ; Gordeuk, Victor R. / Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans. In: American Journal of Tropical Medicine and Hygiene. 1998 ; Vol. 58, No. 3. pp. 358-364.
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