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  • Title: Pharmacokinetics of an extended-dose halofantrine regimen in patients with malaria and in healthy volunteers.
    Author: Ohrt C, Watt G, Teja-Isavadharm P, Keeratithakul D, Loesuttiviboon L, Webster HK, Schuster B, Fleckenstein L.
    Journal: Clin Pharmacol Ther; 1995 May; 57(5):525-32. PubMed ID: 7768075.
    Abstract:
    The pharmacokinetics and tolerance of a 4.5 gm 7-day halofantrine loading dose regimen were evaluated in 10 Thai patients with malaria and in 10 noninfected volunteers. Halofantrine peak plasma concentrations and bioavailability on the first day of treatment were significantly lower in patients with malaria than in healthy volunteers. Halofantrine elimination half-life was significantly shorter in patients with malaria than healthy control subjects (9.5 versus 15.8 days). These data show a distinct effect of acute malaria on the absorption and elimination of the drug. In addition, marked intersubject and intrasubject variability in peak and trough halofantrine levels was observed, indicating variable drug absorption. This dosing regimen was effective and well tolerated, with mild transient diarrhea during the first few days of treatment in both groups. To produce consistently effective drug levels, the currently recommended dosing regimens may be suboptimal. Slow halofantrine elimination raises concern for induction of parasite resistance when the drug is used in endemic areas of the world.
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