1921
Volume 84, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

This randomized, open-label study of patients in India with visceral leishmaniasis (VL) investigated the effect of food on sitamaquine and desethyl-sitamaquine pharmacokinetics. Patients were randomized to receive oral sitamaquine, 2 mg/kg/day, once a day for 21 days across four cohorts (n = 41) (fasted/fed, fed/fasted, fed/fed, and fasted/fasted) over two periods (days 1−10 and 11−21), or intravenous amphotericin B (AmB), 1 mg/kg every other day for 30 days (n = 20). Mean day 21 pharmacokinetics across the four cohorts were sitamaquine, area under curve (AUC) = 6,627−8,903 ng.hr/mL, AUC = 4,859−6,633 ng.hr/mL, maximum plasma concentration ( ) = 401−570 ng/mL, apparent terminal half-life ( ) = 18.3−22.8 hr, time to reach ( ) = 3.5−6 hr; and desethyl-sitamaquine, AUC = 2,307−3,163 ng.hr/mL, = 109−154 ng/mL, = 23.0−27.9 hr, = 2−10 hr, with no significant food effect. On-therapy adverse events were observed for sitamaquine in 4 (10%) of 41 patients and for AmB in 17 (85%) of 20 patients. The final clinical cure (day 180) was 85% (95% confidence interval = 70.8–94.4%) for sitamaquine and 95% (95% confidence interval = 75.1–99.9) for AmB. Sitamaquine can be taken regardless of food intake, was generally well tolerated, and showed potential efficacy in patients with visceral leishmaniasis.

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2011-06-01
2017-11-25
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  • Received : 18 Jul 2010
  • Accepted : 17 Feb 2011

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