Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 2003
Randomized Controlled Trial Clinical TrialPeripheral and central antihyperalgesic effects of diclofenac in a model of human inflammatory pain.
Experimental evidence suggests that the antihyperalgesic effect of nonsteroidal anti-inflammatory drugs may include both peripheral (inflammatory site) and central sites of action. The aim of this study was to assess peripheral and central antihyperalgesic effects of diclofenac in a human experimental pain model. ⋯ The higher antihyperalgesic efficacy of oral diclofenac as compared with topical diclofenac at comparable tissue concentrations suggests that not only peripheral but also central mechanisms are involved in the antihyperalgesic effects of systemically administered diclofenac.
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Clin. Pharmacol. Ther. · Apr 2003
Randomized Controlled Trial Clinical TrialEffects of three fluoroquinolones on QT interval in healthy adults after single doses.
A clinical trial was conducted in healthy adult volunteers to assess the effect of levofloxacin, moxifloxacin, and ciprofloxacin on the QT and QTc interval. ⋯ A change in QTc (Bazett) interval from baseline can be demonstrated safely in healthy volunteers after single high doses of fluoroquinolones that achieve approximately 1.5 times the maximum plasma drug concentration that occurs after recommended doses. There is substantial daily variation in both QT and QTc interval, and the magnitude and frequency of changes in QTc interval can depend on the methods used. These factors need to be considered because clinical trials measuring the effects of drugs on QT intervals are used to estimate the risk of using these drugs. Greater changes in QT and QTc intervals after treatment with moxifloxacin compared with levofloxacin or ciprofloxacin are consistent with in vitro observations related to the effect of these drugs on rapid potassium (IK(r)) channels. The clinical relevance of these differences is not known.
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Clin. Pharmacol. Ther. · Jan 2003
Randomized Controlled Trial Clinical TrialAnalgesic effects of morphine and morphine-6-glucuronide in a transcutaneous electrical pain model in healthy volunteers.
Our objective was to quantify the extent and time course of the effects of morphine-6-glucuronide and morphine on pain threshold, pain tolerance, pupil diameter, and side effects. ⋯ Morphine-6-glucuronide clearly produced analgesic effects in healthy volunteers. However, the high amounts of systemic morphine-6-glucuronide needed to produce the same effects as morphine suggest that morphine-6-glucuronide barely contributes to the central nervous opioid effects after administration of analgesic doses of morphine.
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Clin. Pharmacol. Ther. · Dec 2002
Randomized Controlled Trial Clinical TrialPopulation pharmacokinetic and pharmacodynamic modeling of propofol for long-term sedation in critically ill patients: a comparison between propofol 6% and propofol 1%.
A population pharmacokinetic and pharmacodynamic model of propofol for long-term sedation in critically ill patients is described, because limited information is available in these patients. In the models the influence of time-independent covariates, in particular, the propofol formulation (propofol 6% versus propofol 1%), and of time-dependent covariates was investigated. ⋯ The population models in critically ill patients showed no differences in pharmacokinetics or pharmacodynamics between propofol 6% and propofol 1%. TG and T(c) appeared to be significant covariates for elimination clearance. For the pharmacodynamics, when propofol concentrations were between 0.75 and 1.5 mg/L, Ramsay sedation score 6 was most probable (40%-75%) and the probability for Ramsay sedation score 5 was 20% to 40%. Large pharmacodynamic variabilities were observed.
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Clin. Pharmacol. Ther. · Oct 2002
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialPharmacokinetic-pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsis.
We aimed to characterize the pharmacokinetics and pharmacodynamics of drotrecogin alfa (activated) (recombinant human activated protein C) in patients with severe sepsis. ⋯ Plasma concentrations of drotrecogin alfa (activated) attain steady state rapidly after the infusion is started and decline rapidly after the infusion is stopped. The infusion rate should be based on predose body weight and not on any other demographic or baseline clinical covariate.