Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 2001
Randomized Controlled Trial Clinical TrialDifferent effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin.
St John's Wort, a widely used herbal product, is an inducer of CYP3A4 and it decreases blood concentrations of CYP3A4 substrates. The effects of St John's Wort on the pharmacokinetics of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors simvastatin (an inactive lactone pro-drug) and pravastatin were determined in this study. ⋯ This study showed that St John's Wort decreases plasma concentrations of simvastatin but not of pravastatin. Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John's Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver.
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Clin. Pharmacol. Ther. · Nov 2001
Randomized Controlled Trial Clinical TrialEffect of high-dose lansoprazole on intragastic pH in subjects who are homozygous extensive metabolizers of cytochrome P4502C19.
Lansoprazole is mainly metabolized by cytochrome P4502C19 (CYP2C19) in the liver. The effect of lansoprazole is assumed to be insufficient in subjects who are homozygous extensive metabolizers of CYP2C19. This study aimed to examine whether the CYP2C19 genotype status affected the acid-inhibitory effects of lansoprazole and to develop a strategy to overcome this pharmacogenetic problem. ⋯ The effect of lansoprazole on intragastric pH depended significantly on CYP2C19 genotype status. Complete acid inhibition could be achieved by the frequent administration of lansoprazole (eg, 30 mg 4 times daily) in subjects who were homozygous extensive metabolizers. A genotyping test of CYP2C19 status appears useful for prescribing an optimal dosing scheme of lansoprazole.
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Clin. Pharmacol. Ther. · Sep 2001
Randomized Controlled Trial Comparative Study Clinical TrialGender and the placebo analgesic effect in acute pain.
Our objective was to examine the placebo arms from a series of clinical trials in which the post-third molar extraction dental pain model was used to elucidate the time course of the placebo effect and the proportion of the population that are responders, as well as to evaluate whether the placebo analgesic response of female subjects may differ from that of male subjects. ⋯ The results demonstrated no gender difference in response to placebo. These results were obtained from the post-third molar extraction situation, in which the least possible confounding factors were present. To fully establish the generality of this phenomenon, studies should be carried out in other pain models.
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Clin. Pharmacol. Ther. · May 2001
Randomized Controlled Trial Clinical TrialIntravenous magnesium sulfate for bronchial hyperreactivity: a randomized, controlled, double-blind study.
Magnesium has been shown to be helpful in the treatment of acute exacerbations of asthma. Conflicting data exist concerning the effect of magnesium on bronchial hyperreactivity. ⋯ In the magnesium group, 30% of the subjects reached a normal PC(20) compared with 10% in the placebo group. We conclude that intravenous magnesium sulfate significantly improved bronchial hyperreactivity and may serve as an adjunct to standard treatment.
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Clin. Pharmacol. Ther. · Apr 2001
Randomized Controlled Trial Clinical TrialSpecific effect of venlafaxine on single and repetitive experimental painful stimuli in humans.
Tricyclic antidepressants relieve neuropathic pain, and the analgesic properties of tricyclic antidepressants are substantiated in human experimental pain models. It has been speculated that drugs with a selective inhibition of presynaptic reuptake of both serotonin and noradrenaline could have an analgesic effect comparable to the analgesic effect of tricyclic antidepressants. ⋯ Venlafaxine increases the pain tolerance threshold to electrical sural nerve stimulation and the threshold at which pain increases (pain summation). The impact of venlafaxine on pain summation in this experimental pain model on repetitive stimulation may indicate a potential analgesic effect for clinical neuropathic pain.