British journal of clinical pharmacology
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Br J Clin Pharmacol · Apr 2012
Randomized Controlled TrialCeftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations.
The large variability in drug pharmacokinetic disposition has already been described in ICU patients leading to important variations in drugs concentrations. The usual recommended dosage of ceftazidime is not adapted for all ICU situations and ceftazidime should be monitored closely. New recommendations have to be given for some specific cases. ⋯ Our study demonstrated that in ICU patients for a given MDRD, steady-state takes longer to reach in polytrauma patients than in patients with medical or post surgery reasons for admission. Continuous infusion ensures that a higher percentage of patients reaches the target than the same dose given by discontinuous administration and this only depends on MDRD.
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Br J Clin Pharmacol · Mar 2012
Randomized Controlled TrialThe analgesic effect of pregabalin in patients with chronic pain is reflected by changes in pharmaco-EEG spectral indices.
To identify electroencephalographic (EEG) biomarkers for the analgesic effect of pregabalin in patients with chronic visceral pain. ⋯ Changes in spectral indices caused by slowing of brain oscillations were identified as a biomarker for the central analgesic effect of pregabalin. The developed methodology may provide perspectives to assess individual responses to treatment in personalized medicine.
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Br J Clin Pharmacol · Feb 2012
Randomized Controlled TrialAssessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double-blind, placebo- and positive-controlled thorough QT study.
To assess steady-state effects of therapeutic and supra-therapeutic doses of prucalopride on the QT interval using a novel design involving a parallel placebo group with nested crossover for positive control. ⋯ Prucalopride at both therapeutic and supra therapeutic doses has no clinically significant effects on cardiac repolarisation in healthy volunteers.
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Br J Clin Pharmacol · Jan 2012
Randomized Controlled TrialPharmacokinetics and pharmacodynamics following maintenance doses of prasugrel and clopidogrel in Chinese carriers of CYP2C19 variants.
This open-label, two-period, randomized, crossover study was designed to determine the effect of CYP2C19 reduced function variants on exposure to active metabolites of, and platelet response to, prasugrel and clopidogrel. ⋯ Prasugrel demonstrated higher active metabolite exposure and more consistent pharmacodynamic response across all three predicted phenotype groups compared with clopidogrel, confirming observations from previous research that CYP2C19 phenotype plays an important role in variability of response to clopidogrel, but has no impact on response to prasugrel.
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Br J Clin Pharmacol · Aug 2011
Randomized Controlled TrialSB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans.
Receptor antagonists that block the binding of chemokines such as CXCL8 (IL-8) are effective in animals models of neutrophil-mediated inflammation. It has been hypothesized that selective inhibition of neutrophil trafficking and activation may be a useful adjunct for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease or cystic fibrosis. A CXCR1/2 receptor antagonist has shown activity in an ozone challenge model in humans. ⋯ SB-656933 is a CXCR2 antagonist that demonstrates dose-dependent effects on neutrophil activation and recruitment within a well-tolerated dose range. These data suggest that SB-656933 may be an effective agent in neutrophil-predominant diseases.