Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Jun 2006
Comparative Study Clinical TrialSingle and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.
Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. ⋯ As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy volunteers (median and 95% CI for differences: -5.4% [-19.9% to 2.0%] and -19.4% [-45.6% to 0.4%]). Conservatively, a dose adjustment of dexketoprofen trometamol in patients with impaired hepatic function is recommended.
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Methods Find Exp Clin Pharmacol · Jun 2006
Refractory septic shock: efficacy and safety of very high doses of norepinephrine.
The aim of this study was to evaluate the safety, efficacy, and effects of administration of very high doses of norepinephrine (> 4 microg kg(-1) min(-1)) in catecholamine-resistant septic shock. We reviewed the charts of all patients with nonresponding to commonly used norepinephrine doses (< or = 4 microg kg(-1) min(-1)) septic shock from January 1999 to December 2002 in our Surgical Intensive Care Unit. All patients were treated with high norepinephrine doses (> 4 microg kg(-1) min(-1)), after initial resuscitation, so as to achieve a mean arterial pressure higher than or equal to 65 mmHg. ⋯ Administration of high norepinephrine doses in our patients resulted in a survival rate of 33.4%. Management of catecholamine-resistant septic shock patients poses a challenging problem. Administration of very high norepinephrine doses is safe and effective and may improve survival of these patients with otherwise extremely high mortality rates.
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Methods Find Exp Clin Pharmacol · Apr 2006
ReviewTherapeutic potential of cannabinoid receptor ligands: current status.
There are at least two types of cannabinoid receptors, CB1 also named CNR1 and CB2 also named CNR2, both coupled to G proteins. CB1 receptors exist primarily on central and peripheral neurons. CB2 receptors are present mainly on immune cells. ⋯ Following their release, endocannabinoids are removed from the extracellular space and then degraded by intracellular enzymic hydrolysis. CB1/CB2 agonists are already used clinically as antiemetic or to stimulate appetite. Potential therapeutic uses of cannabinoid receptor agonists include the management of multiple sclerosis, spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, vasodilatation that accompanies advanced cirrhosis, and cancer.
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The present study was undertaken to investigate the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on marble-burying behavior in mice in comparison with those of fluvoxamine and clomipramine. Marble-burying test is extensively used as an animal model for obsessive/compulsive disorder. A significant inhibition in marble-burying behavior was observed with paroxetine, at a dose of 10 mg/kg. ⋯ Although clomipramine, a tricyclic antidepressant, caused an inhibition in marble-burying behavior, a high dose of 100 mg/kg was needed to show a significant effect. On the other hand, all the drugs used in the present study showed no significant changes in spontaneous locomotor activity at doses inhibiting marble-burying behavior. In conclusion, it was confirmed that paroxetine has a potent inhibitory effect on marble-burying behavior in mice, and could have a similar antiobsessive/anticompulsive activity in human beings.
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Methods Find Exp Clin Pharmacol · Nov 2005
Ondansetron does not block tramadol-induced analgesia in mice.
Tramadol is a weak opioid agonist and an inhibitor of the reuptake of noradrenaline and serotonin. This study was undertaken to assess a possible pharmacological interaction of ondansetron, a serotonin-3 (5-hydroxytryptamine-3, 5-HT3) antagonist, and tramadol in an animal model for acute pain. Sixty-three male albino mice were randomly given saline, tramadol (10, 20, and 40 mg kg(-1)), ondansetron (1, 2, and 4 mg kg(-1)), or ondansetron (1, 2, and 4 mg kg(-1)) and tramadol (20 mg kg(-1), given 10 min after ondansetron injection) intraperitoneally. ⋯ Tramadol (20 mg kg(-1)) and ondansetron (1, 2, and 4 mg kg(-1)) increased pain threshold levels at all doses (p < 0.001 for 1 and 2 mg kg(-1) ondansetron and p < 0.01 for 4 mg kg(-1) ondansetron). The pain threshold levels of mice given tramadol (20 mg kg(-1)) alone or tramadol and ondansetron (p > 0.05 for 1, 2, and 4 mg kg(-1)) were similar. Our results indicate that ondansetron-a 5-HT3 selective antagonist-does not decrease the analgesic effectiveness of tramadol in mice, which may be the result of different mechanisms involving 5-HT3 receptors.