European journal of clinical pharmacology
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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
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 1996
Randomized Controlled Trial Clinical TrialCodeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects.
Codeine O-demethylation to morphine is catalysed by the genetic polymorphic sparteine oxygenase (CYP2D6). The objective of the present study was to assess the analgesic effect of codeine on different types of experimental pain in relation to sparteine phenotype. ⋯ This study confirms that codeine O-demethylation depends on CYP2D6; it shows that the 6-glucuronidation of morphine is independent of CYP2D6; it supports the theory that the analgesic effect of codeine depends on its O-demethylation; and it indicates that this is probably also the case for the adverse effects. The results lend no support to the suggestion of a non-opioid analgesic effect of codeine.
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Eur. J. Clin. Pharmacol. · Jan 1996
Randomized Controlled Trial Clinical TrialHaemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril.
Levosimendan in a new inodilator drug that sensitizes troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40-50%. The aim of the present, double-blind study was to evaluate the safety of concomitant use of levosimendan and an ACE-inhibiting drug. ⋯ It seems that concomitant treatment with captopril does not change the haemodynamic effects of levosimendan. No adverse haemodynamic interactions were seen.
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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.