INTRODUCTION Lesinurad is a selective uric acid reabsorption inhibitor approved in the United States and Europe for treatment of gout in combination with a xanthine oxidase inhibitor. A maximum tolerated dose study was conducted to determine the lesinurad supratherapeutic dose, followed by a thorough QTc study to characterize the effect of lesinurad on cardiac repolarization. METHODS The maxi...

Kidney failure secondary to renal hemosiderosis has been reported in diseases with intravascular hemolysis, like paroxysmal nocturnal hemoglobinuria, and valvular heart diseases. We present here a case of hemosiderin induced acute tubular necrosis secondary to intravascular hemolysis from Clostridium difficile infection with possible role of supratherapeutic INR. We discuss the pathophysiology,...

AIMS The study was performed to assess the safety of strontium ranelate in accordance with the ICH, E14 guidelines for QT/QT(c) studies. Its primary objective was to compare supratherapeutic repeated dosing of strontium ranelate (4 g day⁻¹ for 15 days) with placebo on the largest time-matched mean QT(c) variation, from baseline to under treatment values, in healthy subjects. METHODS Ninety-si...

AIMS Exenatide has been demonstrated to improve glycaemic control in patients with type 2 diabetes, with no effect on heart rate corrected QT (QTc ) at therapeutic concentrations. This randomized, placebo- and positive-controlled, crossover, thorough QT study evaluated the effects of therapeutic and supratherapeutic exenatide concentrations on QTc . METHODS Intravenous infusion was employed t...

Ivermectin is an antiparasitic drug that has been used as alternative for prophylaxis and treatment of COVID-19 infection. The adverse effects from supratherapeutic doses can include nonneurological neurological symptoms. In this study, we report the case a 52-year old Filipino male with newly diagnosed diabetes mellitus who developed subacute history fever, cough generalized weakness, causing ...

OBJECTIVE The objective of this study was to determine the next-day residual effects of acute and steady-state nighttime dosing of flibanserin on simulated driving performance and cognitive function in healthy premenopausal women. METHODS In this randomized, double-blind, placebo-controlled, four-way crossover study, 72 subjects were treated with either acute oral doses of placebo, zopiclone ...

Metabolism of arachidonic acid (10 microM) into 15(S)-hydroxyl-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE) was proportional to lactate dehydrogenase release from human neutrophils incubated with supratherapeutic concentrations of non-steroidal anti-inflammatory agents. In contrast to others (Vanderhoek, J., and Bailey, J. (1984) J. Biol. Chem. 259, 6752-6756), we report that increased 1...