Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Oct 2004
Protective effect of bupropion on morphine tolerance and dependence in mice.
Possible reversal of morphine-induced tolerance and dependence by bupropion was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. ⋯ On the other hand, acute administration of bupropion (2 or 5 mg/kg) on day 10, i.e., during the expression phase of morphine dependence, reduced the incidence of naloxone-precipitated withdrawal jumps without affecting tolerance to the analgesic effect. In conclusion, results of the present study suggest the potential use of bupropion in tolerance and dependence.
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Methods Find Exp Clin Pharmacol · Dec 2003
Attenuation of renal ischemia-reperfusion injury by trimetazidine: evidence of an in vivo antioxidant effect.
Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antiischemic agent trimetazidine in a rat model of renal ischemia-reperfusion injury. ⋯ The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. Trimetazidine markedly reduced elevated levels of TBARS and significantly attenuated renal dysfunction and morphological changes in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect and the therapeutic potential of trimetazidine, an anti-ischemic agent, in attenuating renal ischemia-reperfusion injury.
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Methods Find Exp Clin Pharmacol · Oct 2003
Multicenter Study Clinical TrialIrinotecan (CPT-11) in metastatic colorectal cancer patients resistant to 5-fluorouracil (5-FU): a phase II study.
The efficacy and toxicity of irinotecan (CPT-11) 350 mg/m(2) i.v. once every 3 weeks was assessed in 60 patients with advanced colorectal cancer (CRC) showing failure to 5-fluorouracil (5-FU) treatment. The overall objective response rate was 13.6% (1 complete response and 4 partial responses) and 25 patients (42.4%) showed stable disease; the median time to disease progression was 4.4 months and the median survival was 10.5 months. ⋯ Grade 3 or 4 diarrhea appeared in 21 of 131 cycles (16.1%), whereas grade 3 or 4 neutropenia appeared in 78 cycles (25.0%). In conclusion, the present phase II study confirms that CPT-11 350 mg/m(2) every 3 weeks is active and well tolerated as second-line chemotherapy for CRC in 5-FU resistant patients.
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Methods Find Exp Clin Pharmacol · Sep 2003
Randomized Controlled Trial Comparative Study Clinical TrialBioavailability of two new formulations of paracetamol, compared with three marketed formulations, in healthy volunteers.
The aim of this study was to compare the main pharmacokinetic characteristics of two new paracetamol formulations, powder sachet and tablet, with that of three commercially available paracetamol formulations: two conventional solid tablets and one effervescent tablet. Twelve healthy volunteers participated in an open, single dose (paracetamol 1,000 mg), randomized, five-way, crossover study. Formulations studied included: formulation A: 2 x 500 mg paracetamol tablets (Laboratorios Belmac S. ⋯ Formulations A, B and E showed significantly shorter tmax than formulation C. The tmax and Cmax values found for formulations A and B were very similar to that found for E, an effervescent tablet formulation. In conclusion, the two new formulations of paracetamol tested in this study were absorbed rapidly after a single oral dose in healthy volunteers, similar to an effervescent paracetamol formulation and significantly faster than two ordinary commercialized paracetamol tablets.
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Methods Find Exp Clin Pharmacol · Jun 2003
Comparative StudyThe antinociceptive effect of tramadol-venlafaxine combination on the paw withdrawal threshold in a rat model of neuropathic pain.
The combination of venlafaxine and tramadol was compared with the single use of these agents to investigate the antinociceptive effect on paw withdrawal latency (PWL) to paw pressure in rats with neuropathic pain. Rats were divided into 4 groups: group 1 received saline (0.2 ml i.p.); group 2 received venlafaxine (22 mg/kg i.p.); group 3 received tramadol (20 mg/kg i.p.); and group 4 received venlafaxine + tramadol. ⋯ A more potent antinociceptive effect was observed in the tramadol + venlafaxine group, beginning at 60 min and lasting for 1 h. The combination of venlafaxine + tramadol was more effective in increasing the pain threshold in this animal model of neuropathic pain than either of these drugs administered alone.