Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Nov 2011
Randomized Controlled TrialA randomized, controlled trial validates a peripheral supra-additive antihyperalgesic effect of a paracetamol-ketorolac combination.
The combination of paracetamol with non-steroidal anti-inflammatory drugs (NSAIDs) is widely used; however, the nature and mechanism of their interaction are still debated. A double-blind, pharmacokinetic/pharmacodynamic, randomized, cross-over, placebo-controlled study was carried out in human healthy volunteers. The aim was to explore the existence of a positive interaction between paracetamol 1 g and ketorolac 20 mg administered intravenously on experimental pain models in human beings. ⋯ No pharmacokinetic interactions were observed. These results suggest a supra-additive pharmacodynamic interaction between paracetamol and ketorolac in an inflammatory pain model. The mechanism of this interaction could mainly rely on a peripheral contribution of paracetamol to the effect of NSAIDs.
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Basic Clin. Pharmacol. Toxicol. · Nov 2011
Randomized Controlled TrialIs electrical brain activity a reliable biomarker for opioid analgesia in the gut?
The effects of morphine on brain potentials after experimental gut pain have never been investigated. This study explored whether multi-channel-evoked brain potentials (EP) and corresponding dipole sources in the brain would reflect the effects of morphine on experimental oesophageal pain. In a crossover study, the effects of oral morphine (30 mg) or corresponding placebo on pain from electrical oesophageal stimulation were tested in 12 healthy male volunteers. ⋯ The length of the vector describing this shift correlated inversely with the magnitude of the subjective pain relief (r = -0.7; p = 0.02). With the potential of becoming a useful biomarker in analgesic trials, the localization of the dipole sources reflected the analgesic action of morphine after pain stimuli of the gut. Even though further evaluation of the method is necessary, it has the potential to be a valid objective biomarker for opioid analgesia.
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Basic Clin. Pharmacol. Toxicol. · Apr 2011
Randomized Controlled TrialPharmacokinetic/pharmacodynamic relationships of transdermal buprenorphine and fentanyl in experimental human pain models.
Pharmacokinetic/pharmacodynamic (PK/PD) modelling can be used to characterize the relationship between dose regimen of opioids, plasma concentration and effect of opioids, which in turn can lead to more rational treatment regimens of pain. The aim of this study was to investigate the concentration-effect relationship for transdermal buprenorphine and fentanyl in experimentally induced pain. Twenty-two healthy volunteers were randomized to receive transdermal patches with fentanyl (25 μg/hr, 72 hr), buprenorphine (20 μg/hr, 144 hr) or placebo. ⋯ Buprenorphine significantly attenuated bone-associated pain, heat pain, nerve growth factor-induced soreness and cold pressor pain. Fentanyl significantly attenuated cold pressor pain for the administered dose regimens. Although the PK/PD relationship for both drugs could be described with similar models, tissue-differentiated analgesic effects between buprenorphine and fentanyl was shown.
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Basic Clin. Pharmacol. Toxicol. · Aug 2010
Randomized Controlled TrialCo-administration of dextromethorphan and morphine: reduction of post-operative pain and lack of influence on morphine metabolism.
We investigated co-analgesic effect of dextromethorphan in adolescent post-operative patients with idiopathic scoliosis. In a double-blind study, 60 patients with ASA physical status I-II were randomised into two groups. Group dextromethorphan (n = 30; age: 15.9 +/- 2.4 years) was given oral dextromethorphan 30 or 45 mg 1 hr before surgery and 8, 20 and 32 hr after operation. ⋯ Dextromethorphan did not influence morphine glucuronidation, in terms of promotion of formation of any morphine glucuronides. In conclusion, in young patients subjected to spine surgery, addition of dextromethorphan to morphine reduced pain only in early post-operative period. In such patients, co-analgesic action of dextromethorphan was not associated with significant changes in plasma levels of morphine metabolites.
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Basic Clin. Pharmacol. Toxicol. · Aug 2009
Randomized Controlled TrialEvoked human oesophageal hyperalgesia: a potential tool for analgesic evaluation?
Hypersensitivity is a common finding in visceral disorders. Therefore, in the development and testing of analgesics for the treatment of visceral pain, it is important to establish an experimental pain model of visceral hypersensitivity. Such a model will mimic the clinical situation to a higher degree than pain models where the receptors and peripheral afferents are briefly activated as with, for example, electrical, thermal, and mechanical stimulations. ⋯ Acid+capsaicin perfusion induced 56% reduction of the pain threshold to heat (P = 0.04), 19% reduction of the pain threshold to electrical stimuli (P < 0.001), 78% increase of the referred pain areas to mechanical stimulation (P < 0.001) and 52% increase of the referred pain areas to electrical stimulus (P = 0.045). All volunteers were sensitised to one or more modalities by acid+capsaicin. The model was able to evoke consistent hyperalgesia and may be useful in future pharmacological studies.