Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Apr 2009
Randomized Controlled TrialThe hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism.
Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. ⋯ In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM compared with EM (P < 0.001). Oxycodone analgesia seems to depend both on oxycodone itself and its metabolite oxymorphone.
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Basic Clin. Pharmacol. Toxicol. · Sep 2007
Randomized Controlled TrialEffects of paracetamol combined with dextromethorphan in human experimental muscle and skin pain.
By combining drugs with different mechanisms of action, synergistic effects may be achieved. The aim of the present experimental pain study was to combine paracetamol with dextromethorphan for synergistic effects. Furthermore, the reproducibility of the pain assessment methods was evaluated. ⋯ There were no statistical differences (all P > 0.05) between paracetamol compared to placebo, and between the effect of paracetamol and dextromethorphan compared to placebo. The acute pain models were not sufficiently sensitive to detect an analgesic effect of paracetamol or the combination with dextromethorphan. The selected dose of dextromethorphan was low as the aim was to use commonly used doses, and a higher dose of dextromethorphan is most likely needed to attenuate the selected pain measures.
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Basic Clin. Pharmacol. Toxicol. · Jun 2006
Randomized Controlled TrialPharmacodynamics of a new ophthalmic mydriatic insert in healthy volunteers: potential alternative as drug delivery system prior to cataract surgery.
Cataract surgery requires a satisfactory degree of mydriasis throughout the entire operation. A phase I, open-labelled, randomised, cross-over trial was conducted in 18 healthy volunteers to compare mydriasis obtained with subsequent administration of phenylephrine 10% and tropicamide 0.5% eyedrops or a new insoluble-matrix retropalpebral ophthalmic insert containing 5.38 mg phenylephrine and 0.28 mg tropicamide. Phenylephrine serum concentrations were measured over 6 hr following each treatment administration. ⋯ No significant bacterial contamination of conjunctiva swab and cultured insert was observed. The new insoluble-matrix retropalpebral ophthalmic mydriatic insert produced similar but delayed effective and prolonged mydriasis as compared to the standard delivery system. In addition to its potential usefulness in patients undergoing cataract surgery, such new ophthalmic delivery system may be an advantage in children who need to undergo fundus photography due to the single administration and excellent tolerance as well.