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 · 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.
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Br J Clin Pharmacol · Apr 2006
Randomized Controlled TrialPlethysmography and impulse oscillometry assessment of tiotropium and ipratropium bromide; a randomized, double-blind, placebo-controlled, cross-over study in healthy subjects.
Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy subjects. ⋯ In addition to spirometry, IOS resistance measurements and sGaw can distinguish between the effects of long- and shortacting anticholinergic effects in healthy subjects.
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Br J Clin Pharmacol · Apr 2006
Randomized Controlled TrialHyperalgesia induced by cutaneous freeze injury for testing analgesics in healthy volunteers.
The early phases of the clinical development of new analgesic agents are severely hindered by a lack of reliable sensitive tests based on experimental pain models. The aim of this study was to assess the ability of a localized hyperalgesia model induced by cutaneous freeze injury to evaluate the pharmacodynamic profile of weak analgesic agents in healthy volunteers. ⋯ Cutaneous freeze injury coupled with a von Frey electronic device to assess the mechanical pain threshold is a convenient model that causes no discomfort. The improved sensitivity and stability of this experimental model of hyperalgesia over three consecutive days make it a useful tool for evaluating the efficacy and detecting the potential sites of action of analgesic agents such as nonsteroidal anti-inflammatory drugs in healthy human subjects.
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Br J Clin Pharmacol · Feb 2006
Randomized Controlled Trial Comparative StudyComparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise.
To compare in humans the effects of ivabradine and propranolol on cardiac and systemic haemodynamics at rest, during tilt and exercise. ⋯ These results demonstrate that for a similar decrease in HR at rest and during sympathetic stimulation, acute administration of ivabradine, a selective heart rate-lowering agent, decreased myocardial oxygen demand to the same extent as a reference beta-blocker, propranolol, but without evidence of depressant effect on cardiac function.