British journal of clinical pharmacology
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Br J Clin Pharmacol · Feb 2018
Randomized Controlled TrialIs tranexamic acid exposure related to blood loss in hip arthroplasty? A pharmacokinetic-pharmacodynamic study.
Tranexamic acid (TXA) is an antifibrinolytic agent, decreasing blood loss in hip arthroplasty. The present study investigated the relationship between TXA exposure markers, including the time above the in vitro threshold reported for inhibition of fibrinolysis (10 mg l-1 ), and perioperative blood loss. ⋯ In hip arthroplasty, TXA plasma concentrations were maintained above 10 mg l-1 during surgery and for a minimum of 3 h with a preoperative TXA dose of 1 g. Keeping TXA concentrations above this threshold up to 16 h conferred no advantage with regard to blood loss.
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Br J Clin Pharmacol · Feb 2018
Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.
Inflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A-mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice. ⋯ The recently published pharmacokinetic model for midazolam, quantifying the influence of maturation, inflammation and organ failure in children, yields unbiased clearance predictions and can therefore be used for dosing instructions in term neonates, children and adults with varying levels of critical illness, including healthy adults, but not for extrapolation to preterm neonates.
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Br J Clin Pharmacol · Jan 2018
Clinical TrialFactor Xa inhibition by rivaroxaban in the trough steady state can significantly reduce thrombin generation.
The aim of the present study was to demonstrate evidence of reduced thrombin generation at the trough plasma rivaroxaban concentration. ⋯ Residual plasma rivaroxaban at the trough steady state may explain the antithrombin effect of rivaroxaban in patients with nonvalvular atrial fibrillation.
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Br J Clin Pharmacol · Jan 2018
Global population pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib in cancer patients: rationale for lower dosage in Asia.
This population pharmacokinetic analysis was conducted to describe quantitatively the regional differences and sources of interpatient variability on the apparent oral clearance of alisertib. ⋯ Model-based simulations support the achievement of similar alisertib exposures in patients in Asia who are administered a 40% lower dose compared with the Western population, thereby providing a quantitative clinical pharmacology bridging and regional dosing rationale for global drug development.
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Br J Clin Pharmacol · Dec 2017
Randomized Controlled Trial Comparative StudyTicagrelor mitigates ischaemia-reperfusion induced vascular endothelial dysfunction in healthy young males - a randomized, single-blinded study.
Animal data suggest that ticagrelor but not clopidogrel protects against tissue injury. It is unclear if this effect of ticagrelor is also detectable in humans. We studied the effect of ticagrelor and clopidogrel at standard clinical doses on endothelial dysfunction in an experimental model of forearm vascular ischaemia-reperfusion (IR) injury. ⋯ Our data indicate that ticagrelor treatment exerts a greater vascular salutary effect than clopidogrel during reperfusion after an acute vascular occlusion. IR-induced vascular injury cannot be prevented completely by administration of these antiplatelet agents at standard clinical doses.