British journal of clinical pharmacology
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Br J Clin Pharmacol · Aug 2017
Population pharmacokinetics and site of action exposures of veliparib with topotecan plus carboplatin in patients with haematological malignancies.
Veliparib is a potent inhibitor of poly(ADP-ribose) polymerase (PARP) enzyme. The objectives of the analysis were to evaluate the effect of baseline covariates and co-administration of topotecan plus carboplatin (T + C) on pharmacokinetics of veliparib in patients with refractory acute leukaemia, and compare veliparib concentration in various biological matrices. ⋯ Consistent with veliparib's physiochemical properties and its elimination mechanism, LBM and CrCL were found to affect pharmacokinetics of veliparib while concomitant administration of T + C did not affect veliparib's CL/F. Plasma concentrations were found to be a reasonable surrogate for veliparib concentrations in peripheral blood and bone marrow supernatant but not blasts. The current model will be utilized to conduct exposure-response analysis to support dosing recommendations.
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Br J Clin Pharmacol · Aug 2017
Comparative StudyRisk of major bleeding and stroke associated with the use of vitamin K antagonists, nonvitamin K antagonist oral anticoagulants and aspirin in patients with atrial fibrillation: a cohort study.
Nonvitamin K antagonist oral anticoagulants (NOACs) are now available for the prevention of stroke in patients with atrial fibrillation (AF) as an alternative to vitamin K antagonists (VKA) and aspirin. The comparative effectiveness and safety in daily practice of these different drug classes is still unclear. The objective of this study was to evaluate the risk of major bleeding and stroke in AF patients using NOACs, VKAs or aspirin. ⋯ NOACs were associated with a higher risk on gastrointestinal bleeding, particularly in women. The use of NOACs in patients who are vulnerable for this type of bleeding should be carefully considered. NOACs and VKAs are equally effective in preventing stroke. Aspirin was not effective in the prevention of stroke in AF.
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Br J Clin Pharmacol · Jul 2017
Review Meta AnalysisEfficacy of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting: a meta-analysis.
The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV). ⋯ Olanzapine is an excellent alternative for the prophylaxis of CINV. Olanzapine 5 mg per day should be recommended as the initial dose because of equivalent efficacy to a 10 mg dose but a lower potential risk of side effects. Further studies are needed to explore the optimal combination of medicines.
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Br J Clin Pharmacol · Jul 2017
Randomized Controlled TrialRemote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomized controlled crossover pilot study.
The aim of this article is to test the hypothesis that remote ischaemic preconditioning (RIPC) increases circulating endogenous local and systemic plasma (nitrite) during RIPC and ischaemia-reperfusion (IR) as a potential protective mechanism against ischaemia-reperfusion injury (IRI). ⋯ RIPC had no effect on plasma (nitrite) during the RIPC sequence, but instead decreased plasma (nitrite) by ~25% during IR. This would likely counteract the protective mechanisms of RIPC, and contribute to RIPC's lack of efficacy, as observed in recent clinical trials. A combined approach of RIPC with nitrite administration may be required.
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Br J Clin Pharmacol · Jul 2017
Investigation of the predictive validity of laser-EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers.
The aim of the present study was to assess the predictivity of laser-(radiant-heat)-evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti-nociceptive/anti-hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types. ⋯ LEP algesimetry is sensitive to analgesics with different modes of action and may enable the effects of novel analgesics to be assessed during early clinical development.