British journal of clinical pharmacology
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Br J Clin Pharmacol · Nov 2019
Vancomycin is commonly under-dosed in critically ill children and neonates.
Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume of distribution. Therapeutic drug monitoring (TDM) is recommended to achieve vancomycin trough concentrations between 10 and 20 mg/L. In this study we reviewed vancomycin dosing, TDM and treatment outcomes in paediatric and neonatal intensive care unit patients. ⋯ In critically ill children, individualised dosing is needed. In the absence of Bayesian model-based dosing, in children with normal renal function, empiric vancomycin doses of at least 30 mg/kg/day in neonates of <35 weeks corrected gestational age, and 50 mg/kg/day in older children, should be considered. Optimisation of TDM practices through the development of protocols, ideally built into electronic medical records, should be considered.
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Br J Clin Pharmacol · Sep 2019
Randomized Controlled Trial Multicenter StudyEffects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite.
Quizartinib is an oral, highly potent and selective next-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor under investigation in patients with FLT3-internal tandem duplication-mutated acute myeloid leukaemia. This drug-drug interaction study assessed the pharmacokinetics (PK) of quizartinib when coadministered with strong or moderate cytochrome P450 3A (CYP3A) inhibitors. ⋯ These results suggest reducing the dose of quizartinib when coadministered with a strong CYP3A inhibitor, but not with a moderate or weak CYP3A inhibitor. This dose reduction was implemented in phase 3 evaluation of quizartinib.
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Br J Clin Pharmacol · Sep 2019
Multicenter StudyOptimal route for administering tranexamic acid in primary unilateral total hip arthroplasty: Results from a multicenter cohort study.
This study aimed to compare the efficacy and safety of different tranexamic acid (TXA) routes following primary total hip arthroplasty (THA). ⋯ TXA is effective and safe to decrease blood loss and transfusion following primary THA, regardless of whether it is administered intravenously, topically or both. Intravenous or combined routes may produce better haemostatic effects, so they may be suggested in the absence of contraindications.
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Br J Clin Pharmacol · Jul 2019
Randomized Controlled TrialA randomized double-blind, placebo-controlled clinical phase IIa trial on safety, immunomodulatory effects and pharmacokinetics of EA-230 during experimental human endotoxaemia.
EA-230 is a human chorionic gonadotropin hormone-derived linear tetrapeptide, developed for the treatment of systemic inflammation-related disorders. EA-230 has shown promising immunomodulatory and tissue-protective effects in animals and an excellent safety profile in human phase I studies that we performed. The present phase IIa study follows-up on these results by investigating the safety, efficacy and pharmacokinetics of EA-230 under systemic inflammatory conditions induced by experimental human endotoxaemia. ⋯ Administration of EA-230 is safe and results in attenuation of the systemic inflammatory response in humans.