British journal of clinical pharmacology
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Br J Clin Pharmacol · Sep 2014
Multicenter StudyEffect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment.
In September 2012 the UK's Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single '100 mg l(-1) ' nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning. ⋯ The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning.
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Br J Clin Pharmacol · Sep 2014
ReviewThiopurine monitoring in children with inflammatory bowel disease: a systematic review.
The aim was to systematically review the evidence on the clinical usefulness of thiopurine metabolite and white blood count (WBC) monitoring in the assessment of clinical outcomes in children with inflammatory bowel disease (IBD). ⋯ Thiopurine metabolite testing does not safely predict clinical outcome, but may facilitate toxicity surveillance and treatment optimization in poor responders. Current evidence favours the combination of thiopurine metabolite/WBC monitoring and clinic follow-up for prompt identification of haematologic/hepatic toxicity safe dose adjustment, and treatment modification in cases of suboptimal clinical outcome or non-compliance. Well designed RCTs for the identification of robust surrogate markers of thiopurine efficacy and toxicity are required.
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Br J Clin Pharmacol · Sep 2014
Concomitant oral and intravenous pharmacokinetics of trametinib, a MEK inhibitor, in subjects with solid tumours.
The aim of this phase 1, single centre, open label study in four patients with solid tumours was to determine the absolute bioavailability of a 2 mg oral dose of trametinib. Trametinib is an orally bioavailable, reversible and selective allosteric inhibitor of MEK1 and MEK2 activation and kinase activity. ⋯ Trametinib absolute bioavailability was moderate to high, whereas first pass metabolism was low.