PHARMACOKINETICS OF AN EXTENDED-DOSE HALOFANTRINE REGIMEN IN PATIENTSWITH MALARIA AND IN HEALTHY-VOLUNTEERS

The pharmacokinetics and tolerance of a 4.5 gm 7-day halofantrine load ing dose regimen were evaluated in 10 Thai patients with malaria and i n 10 noninfected volunteers. Halofantrine peak plasma concentrations a nd bioavailability on the first day of treatment were significantly lo wer in patients with malaria than in healthy volunteers. Halofantrine elimination half-life was significantly shorter in patients with malar ia than healthy control subjects (9.5 versus 15.8 days). These data sh ow a distinct effect of acute malaria on the absorption and eliminatio n of the drug. In addition, marked intersubject and intrasubject varia bility 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 t reatment in both groups. To produce consistently effective drug levels , the currently recommended dosing regimens may be suboptimal. Slow ha lofantrine elimination raises concern for induction of parasite resist ance When the drug is used in endemic areas of the world.