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Clinical Efficacy and Pharmacokinetics of Micronized Halofantrine for the Treatment of Acute Uncomplicated Falciparum Malaria in Nonimmune Patients
O. Bouchaud
O. Bouchaud
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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L. K. Basco
L. K. Basco
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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C. Gillotin
C. Gillotin
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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F. Gimenez
F. Gimenez
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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O. Ramiliarisoa
O. Ramiliarisoa
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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B. Genissel
B. Genissel
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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E. Bouvet
E. Bouvet
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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R. Farinotti
R. Farinotti
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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J. Le Bras
J. Le Bras
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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J. P. Coulaud
J. P. Coulaud
Department of Infectious and Tropical Diseases, Department of Parasitology, and Department of Clinical Pharmacy, Hospital Bichat-Claude Bernard, Department of Clinical Pharmacokinetics, Hopital Pitie-Salpetriere, Paris, France
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Twenty-eight nonimmune patients with acute uncomplicated falciparum malaria returning from subSaharan Africa were treated with a micronized formulation of halofantrine hydrochloride (three doses of 250 mg at 6-hr intervals) to investigate the drug's efficacy, tolerance, and pharmacokinetics. In vitro drug susceptibility patterns were determined by the isotopic semimicrotest. Twenty-four of 28 patients were cured. Two of the four patients experiencing recrudescence were associated with low absorption of the drug and parasites susceptible in vitro to halofantrine. The other two patients had adequate plasma concentrations of halofantrine and its main human metabolite, N-desbutylhalofantrine, but the isolates were also resistant in vitro to the drugs, suggesting drug resistance as the cause of treatment failure. Only mild, transitory side effects were noted. A wide interindividual variation in plasma concentrations of halofantrine and its metabolite was observed. Pharmacokinetic studies suggested that the micronized formulation of halofantrine hydrochloride may not increase drug absorption considerably. Further studies using higher doses or longer treatment periods are needed to ensure that adequate plasma concentrations of the drug are used.
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| Past two years | Past Year | Past 30 Days | |
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