British journal of clinical pharmacology
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Br J Clin Pharmacol · Jul 2010
Randomized Controlled TrialEltrombopag does not affect cardiac repolarization: results from a definitive QTc study in healthy subjects.
Some non-anti-arrhythmic drugs delay cardiac repolarization, which can be measured as an increase in the QT interval. Delays in cardiac repolarization create an electrophysiological environment that favours the development of cardiac arrhythmias, which may lead to torsade de pointes, which can be fatal. As part of the clinical development of eltrombopag, a thorough QT(c) study was conducted to evaluate the effects of eltrombopag on cardiac repolarization at both therapeutic and supratherapeutic doses and to characterize the relationship between plasma eltrombopag concentrations and change in QT(c). ⋯ No clinically significant QT(c) prolongation was observed for eltrombopag at therapeutic and supratherapeutic doses.
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Br J Clin Pharmacol · Jul 2010
Randomized Controlled Trial Comparative StudyPharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers.
The antiplatelet agent clopidogrel is currently the recommended treatment for acute coronary syndrome (ACS). Inhibition of platelet aggregation (IPA) with clopidogrel is insufficient, which increases the risk for recurrent ischaemic events. Therefore, there is a need for antiplatelet agents with improved IPA. Ticagrelor (AZD6140) is a new antiplatelet agent in clinical development for reduction of thrombotic events in patients with ACS. ⋯ Multiple dosing provided predictable pharmacokinetics of ticagrelor and its metabolite over the dose range of 50-600 mg once daily and 50-300 mg twice daily with C(max) and AUC(0,t) increasing approximately dose-proportionally. Greater and more consistent IPA with ticagrelor at doses > or = 100 mg twice daily and > or = 300 mg once daily were observed than with clopidogrel. Ticagrelor at doses up to 600 mg day(-1) was well tolerated.