British journal of clinical pharmacology
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Br J Clin Pharmacol · Jan 2019
ReviewHyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis: a clinical pharmacological perspective on a surgical procedure.
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care in the treatment of patients with peritoneal carcinomatosis of colorectal origin. The use of oxaliplatin for HIPEC has gained popularity. ⋯ Clinicians should be aware of the clinical importance of oxaliplatin pharmacology when performing HIPEC surgery. This review adds new insights into the complex field of the pharmacology of HIPEC and highlights an important worldwide problem: the lack of standardization of the HIPEC procedure.
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Br J Clin Pharmacol · Nov 2016
ReviewTargeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders.
Neurodegenerative disorders are significantly increasing in incidence as the age of the global population continues to climb with improved life expectancy. At present, more than 30 million individuals throughout the world are impacted by acute and chronic neurodegenerative disorders with limited treatment strategies. ⋯ Coupled to the cellular biology of mTOR are a number of considerations for the development of novel treatments involving the fine control of mTOR signalling, tumourigenesis, complexity of the apoptosis and autophagy relationship, functional outcome in the nervous system, and the intimately linked pathways of growth factors, phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), AMP activated protein kinase (AMPK), silent mating type information regulation two homologue one (Saccharomyces cerevisiae) (SIRT1) and others. Effective clinical translation of the cellular signalling mechanisms of mTOR offers provocative avenues for new drug development in the nervous system tempered only by the need to elucidate further the intricacies of the mTOR pathway.
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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.
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Br J Clin Pharmacol · Apr 2017
Randomized Controlled Trial Multicenter StudyRandomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.
No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. ⋯ The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism.
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Br J Clin Pharmacol · Apr 2016
Clinical TrialParacetamol decreases steady-state exposure to lamotrigine by induction of glucuronidation in healthy subjects.
Patients receiving lamotrigine therapy frequently use paracetamol concomitantly. While one study suggests a possible, clinically relevant drug-drug interaction, practical recommendations of the concomitant use are inconsistent. We performed a systematic pharmacokinetic study in healthy volunteers to quantify the effect of 4 day treatment with paracetamol on the metabolism of steady-state lamotrigine. ⋯ Paracetamol statistically significantly induced steady-state lamotrigine glucuronidation, resulting in a 20% decrease in total systemic exposure and a 25% decrease in trough value of lamotrigine. This interaction may be of clinical relevance in some patients.