Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Oct 2006
Randomized Controlled Trial Multicenter StudyImpact of ibuprofen administration on renal drug clearance in the first weeks of life.
The administration of ibuprofen or any other nonselective cyclooxygenase (COX) inhibitor drug in early neonatal life is associated with a reduction of glomerular filtration, which reduces the elimination of drugs dependent on renal function for clearance. However, the relationship between COX inhibitor drug indication (prophylactic or therapeutic) and the magnitude of this effect remains unclear. ⋯ A significant and clinically relevant reduction in drug clearance is observed when ibuprofen is coadministered independent of indication, postmenstrual or postnatal age. Population modeling with covariate analyses can provide us with the tools to further disentangle the impact of nonselective COX-inhibitors on renal drug clearance.
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Methods Find Exp Clin Pharmacol · Oct 2006
Controlled Clinical TrialThe effect of propofol as an antioxidant agent in intravenous regional anesthesia.
Intravenous regional anesthesia (IVRA) is a technique whereby a tourniquet is used to restrict blood flow to an exsanguinated limb. Propofol was shown to attenuate ischemia-reperfusion damage. We aimed to investigate the effect of low-dose propofol as an antioxidant in this process. ⋯ However, in Group P, serum levels of MDA after the release of the tourniquet periods were significantly lower than that before the release of the tourniquet (p < 0.05). The addition of propofol (20 mg) to lidocaine for IVRA inhibits MDA levels. We conclude that the addition of propofol to lidocaine can be considered as a useful antioxidant in this type of anesthesia.
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Methods Find Exp Clin Pharmacol · Sep 2006
Randomized Controlled TrialThe effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A randomized, double-blind, placebo-controlled study.
The metabolism of melatonin to 6-sulphatoxymelatonin (aMT6S) and N-acetylserotonin (NAS) is catalyzed by cytochrome-P450 (CYP) isozymes CYP1A2 and CYP2C19 respectively. We studied the in vivo effect of CYP2C19 substrate (citalopram, omepratzole, or lansopratzole) on the metabolism of endogenous and exogenous melatonin by measuring the excretion of urinary aMT6S, the main metabolite of melatonin, and a reliable estimate of plasma melatonin in 15 insomniac psychogeriatric inpatients. The effect of melatonin treatment on sleep parameters was also assessed. ⋯ The sleep parameters in the patients on melatonin treatment did not differ from those in the patients treated with placebo. In conclusion, it may be inferred that CYP2C19 substrate slows the metabolism of exogenous melatonin and increases its bioavailability, as shown by the augmented excretion of aMT6S, probably by inhibiting the conversion of melatonin to NAS via CYP2C19 isozyme. Melatonin therapy may not affect the sleep parameters in our psychogeriatric inpatients.
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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.