European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jan 1997
Randomized Controlled Trial Clinical TrialThe negative mucosal potential: separating central and peripheral effects of NSAIDs in man.
We wanted to test whether assessment of both a central pain-related signal (chemo-somatosensory evoked potential, CSSEP) and a concomitantly recorded peripheral signal (negative mucosal potential, NMP) allows for separation of central and peripheral effects of NSAIDs. For this purpose, experimental conditions were created in which NSAIDs had previously been observed to produce effects on phasic and tonic pain by either central or peripheral mechanisms. ⋯ As described earlier, administration of ibuprofen was followed by a decrease in tonic pain but-relative to placebo-an increase in correlates of phasic pain, indicating a specific effect of ibuprofen on the interaction between the pain stimuli under these special experimental conditions. Based on the similar behaviour of CSSEP and NMP, it was concluded that the pharmacological process underlying this phenomenon was localised in the periphery. By means of the simultaneous recording of interrelated peripheral and central electrophysiologic correlates of nociception, it was possible to separate central and peripheral effects of an NSAID. The major advantage of this pain model is the possibility of obtaining peripheral pain-related activity directly using a non-invasive technique in humans.
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Eur. J. Clin. Pharmacol. · Jan 1997
Randomized Controlled Trial Multicenter Study Clinical TrialEvaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever.
We compared efficacy and impact on the comfort of ibuprofen (7.5 mg/kg per dose), aspirin (10 mg/kg/dose) and paracetamol (10 mg/kg per dose) on children with fever aged 6-24 months in an open, randomised study with three parallel groups. ⋯ The efficacy of ibuprofen was better than that of aspirin or paracetamol. In spite of more adverse events, the comfort scores were significantly in favour of ibuprofen 6 h after the first dose of treatment.
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Eur. J. Clin. Pharmacol. · Jan 1997
Effects and pharmacokinetics of high dose metoprolol on chest pain in patients with suspected or definite acute myocardial infarction.
Pain intensity and the plasma concentrations of metoprolol and its major metabolite alpha-hydroxymetoprolol as well as noradrenaline (NA), adrenaline (A) and neuropeptide Y (NPY) were determined in patients with pain due to definite or suspected acute myocardial infarction (AMI) after graded metoprolol infusion. Pain intensity and metoprolol kinetics were assessed over 8 h. ⋯ High-dose intravenous metoprolol was well tolerated in patients with suspected AMI. There was a more rapid and almost complete pain relief in patients without signs of transmural ischaemia compared with the patients with ECG signs of transmural AMI at arrival. In the later group of patients, plasma clearance of metoprolol was significantly reduced.
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Eur. J. Clin. Pharmacol. · Jan 1996
Randomized Controlled Trial Clinical TrialDose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.
The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. ⋯ This investigation confirms that paroxetine and fluoxetine are potent inhibitors of CYP2D6, that fluvoxamine and fluoxetine are moderate inhibitors of CYP2C19 and that fluvoxamine is a potent inhibitor of CYP1A2 in humans in vivo. The clinical prediction of interaction from single-dose experiments may have to take the degree of accumulation during steady-state after multiple doses into account.
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Eur. J. Clin. Pharmacol. · Jan 1996
Clinical Trial Controlled Clinical TrialImpact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake.
The analgesic effect of codeine depends on its O-demethylation to morphine via sparteine oxygenase (CYP2D6) in the liver and presumably also via this enzyme in the CNS. We studied the ability of quinidine, which is a potent inhibitor of CYP2D6, to penetrate the blood brain barrier and its possible impact on codeine O-demethylation in CNS. ⋯ Quinidine penetrates the blood brain barrier poorly, but quinidine pre-treatment leads to pronounced lowering of the cerebrospinal fluid concentration of morphine after codeine intake. However, the O-demethylation of codeine in CNS may not be totally blocked by quinidine.