Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Jun 2006
Clinical TrialClinical pharmacokinetics of parenteral dexketoprofen trometamol in healthy subjects.
Dexketoprofen trometamol, a highly water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug used for pain relief. Two studies were conducted to determine the pharmacokinetics of the drug in healthy subjects following single intravenous (i.v.) and intramuscular (i.m.) doses of dexketoprofen. In the first study, 6 male and 6 female volunteers received 50 mg dexketoprofen (74 mg dexketoprofen trometamol) by i.v. bolus. ⋯ No significant differences by gender were obtained following both parenteral routes. A dose proportionality in Cmax and AUC0-x was observed. Dexketoprofen pharmacokinetics following i.v. and i.m. routes, together with the availability of a single 2 ml formulation, allows for a potential advantageous rapid switch to the oral formulation when clinically possible.
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Methods Find Exp Clin Pharmacol · Jun 2006
Comparative Study Clinical TrialSingle and repeated dose pharmacokinetics of dexketoprofen trometamol in young and elderly subjects.
Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) widely used for pain relief. This study was conducted to determine the pharmacokinetics of this analgesic agent in elderly subjects and to compare them with young volunteers following single and repeated oral doses. Twelve healthy young and 12 elderly subjects received 25 mg oral dexketo- profen (equivalent to 37 mg of its tromethamine salt) as a single dose (day 1) and 3-day repeated doses (1 dose every 8 h for a total of 10 doses). ⋯ Cumulative excretions in urine up to 24 h of unbound, conjugated and total dexketoprofen were similar among the groups. These results suggest that dexketoprofen elimination is reduced in the elderly. Although no drug accumulation in plasma was observed after single and repeated dosing, the renal function decline in elderly patients calls for a cautious dose-adjustment in this population.
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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.