کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8514489 1556508 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of ABT-493: A First-In-Human Study
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of ABT-493: A First-In-Human Study
چکیده انگلیسی
ABT-493 is a hepatitis C virus nonstructural protein 3/4A protease inhibitor with pangenotypic antiviral activity. This study investigated the pharmacokinetics, safety, and tolerability of single and multiple ascending doses of ABT-493 and the effect of food and ritonavir coadministration on ABT-493 pharmacokinetics in healthy adults. In the blinded, randomized, placebo-controlled phase 1 single- and multiple-dose portions of the study, ABT-493 25-800 mg were evaluated as single doses, and 200, 400, and 800 mg were evaluated as multiple doses. The effect of food and ritonavir was assessed in a crossover unblinded fashion. ABT-493 pharmacokinetic parameters were estimated using noncompartmental methods. ABT-493 25-800 mg showed a greater than dose-proportional increase in exposures. Minimal accumulation (≤15%) was observed after ABT-493 200- and 400-mg multiple dosing; higher accumulations (approximately 80%) were observed after the 800-mg dose. ABT-493 harmonic mean half-life was 6-9 hours. Food had a minimal effect on ABT-493 exposures. All adverse events were assessed by the investigator as mild to moderate in severity, no serious adverse events were reported, and no subjects discontinued from the study. No clinically significant laboratory tests, vital signs, or electrocardiogram values were reported. A maximum tolerated dose was not reached.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 2, February 2017, Pages 645-651
نویسندگان
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