کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8513173 1556490 2018 44 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Repurposing of Ivermectin for Malaria: A Prospective Pharmacokinetics-Based Virtual Clinical Trials Assessment of Dosing Regimen Options
ترجمه فارسی عنوان
بازپرداخت ایورمکتین برای مالاریا: یک آزمایشگاه بالینی مجازی مبتنی بر فارماکوکینتیک چشم انداز ارزیابی گزینه های رژیم دوز
کلمات کلیدی
فارماکوکینتیک مبتنی بر فیزیولوژی، فارماکوکینتیک، مقاومت دارویی، اونیکومیکوزیس، در مدل سازی سیلیکا،
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی
Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance, attention has turned toward ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiology-based pharmacokinetic model in healthy adults (20-50 years), pediatric (3-5 years/15-25 kg) subjects, and a representative adult malaria population group (Thailand). Dosing optimization demonstrating a twice-daily dose for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and pediatric subjects. Furthermore, to address the occurrence of CYP450 induction that is often encountered with antiretroviral agents, simulated drug-drug interaction studies with efavirenz highlighted that a 1-mg/kg once-daily dose for 5 days would counteract the increased ivermectin hepatic clearance and enable a time above LC50 of 138.8 h in adults and 141.2 h in pediatric subjects. It was also demonstrated that dosage regimen design would require consideration of the age-weight geographical relationship of the subjects, with a dosage regimen for a representative Thailand population group requiring at least a single daily dose for 5 days to maintain ivermectin plasma concentrations and a time above LC50 similar to that in healthy adults.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 8, August 2018, Pages 2236-2250
نویسندگان
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