British journal of clinical pharmacology
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Br J Clin Pharmacol · May 2007
Randomized Controlled TrialEvaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in Type 2 diabetes mellitus patients and healthy volunteers.
* Many studies have investigated the effects of thiazolidinediones on isolated biochemical markers (biomarkers) or sets of markers in Type 2 diabetes mellitus (T2DM) patients and healthy volunteers. * However, a limited number of parameters is not capable of capturing the broad response to pharmacological intervention with these types of (pleiotropic) drugs, which are known to activate the nuclear transcription factor peroxisome proliferator activated receptor gamma (PPARgamma). * Our study tested the new hypothesis (primary objective) that nuclear magnetic resonance (NMR)-based metabolomics, capable of providing a readout of global metabolite concentrations in biofluids, could provide a better (more holistic) picture of the the multiparametric response to pharmacological intervention with a PPARgamma agonist and thus yield a broad array of biomarkers ('fingerprint') that could be used to support and expedite clinical development of novel thiazolidinediones. ⋯ The results of this study indicate that NMR-based metabolomics of urine and blood plasma samples can yield a broad array of early responding biomarkers for the effects of RSG in T2DM patients, as well as nonglucose biomarkers that may reflect the T2DM state.
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Br J Clin Pharmacol · Mar 2007
ReviewDose-response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies.
Establishing the dose-response relationship for clinically useful doses of aspirin, ibuprofen and paracetamol has been difficult. Indirect comparison from meta-analysis is compromised by too little information at some doses. ⋯ Use of trials making direct comparison of two different doses of target drugs revealed the underlying dose-response curve for clinical analgesia.
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Br J Clin Pharmacol · Feb 2007
In-hospital cardiac arrest is associated with use of non-antiarrhythmic QTc-prolonging drugs.
QTc interval-prolonging drugs have been linked to cardiac arrhythmias, cardiac arrest and sudden death. In this study we aimed to quantify the risk of cardiac arrest associated with the use of non-antiarrhythmic QTc-prolonging drugs in an academic hospital setting. ⋯ Use of non-antiarrhythmic QTc-prolonging drugs in hospitalized patients with several underlying disease is associated with an increased risk of cardiac arrest. The effect is dose related and pharmacokinetic drug-drug interactions increase the risk substantially. Physicians caring for inpatients should be made aware of the fact that these non-antiarrhythmic drugs may be hazardous, so that potential risks can be weighed against treatment benefits and additional cardiac surveillance can be requested, if necessary.
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Br J Clin Pharmacol · Jan 2007
Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance.
*Effects of size, renal function, age (postnatal age, gestational age and postmenstrual age) as predictors of vancomycin clearance in premature neonates are established, but the relative contribution of each component remains poorly quantified, largely because these variables are closely correlated. *We have quantified the covariates contributing to vancomycin clearance population parameter variability in order to establish the major covariates required for dosing predictions. Size, standardized using allometric models, was the primary covariate used in our analysis. ⋯ Size, renal function and PMA are the major contributors to clearance variability in premature neonates. The small (18%) unexplained variability in clearance suggests target concentration intervention is unnecessary if size, age and renal function are used to predict the dose. Extrapolation to an adult clearance from neonatal data is possible using allometric size models and a function describing clearance maturation.
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Br J Clin Pharmacol · Jan 2007
Randomized Controlled TrialComparative bioequivalence study between a novel matrix transdermal delivery system of fentanyl and a commercially available reservoir formulation.
To determine the pharmacokinetics, safety and performance of a novel matrix formulation of fentanyl. ⋯ The two formulations are expected to result in similar efficacy for the management of severe pain.