Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Dec 2012
Randomized Controlled TrialEffect of an anesthesia with propofol compared with desflurane on free radical production and liver function after partial hepatectomy.
Propofol has shown antioxidant properties, but no study has focused on liver resection surgery. The aim of this study was to investigate the effect of an anesthesia with propofol compared with desflurane on oxidative stress and hepatic function during and after partial hepatectomy. This was a prospective randomized study performed on two parallel groups. ⋯ Plasma levels of α-GST at 120 min were lower in propofol than in desflurane group (142.2 ± 75.4 vs. 205.7 ± 66.5, P = 0.023), and MEGX on day 2 was higher (0.092 ± 0.096 vs. 0.036 ± 0.020, P = 0.007). No differences between groups were observed with regard to plasma levels of aminotransferases, prothrombin time, and plasma factor V. Our study showed that in patients undergoing partial hepatectomy, propofol did not reduce MDA formation but seemed to display a protective effect on hepatic damages and liver function when compared to desflurane.
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Fundam Clin Pharmacol · Dec 2012
Randomized Controlled TrialEvaluation of the effect of one large dose of erythropoietin against cardiac and cerebral ischemic injury occurring during cardiac surgery with cardiopulmonary bypass: a randomized double-blind placebo-controlled pilot study.
Cardiac surgery and cardiopulmonary bypass (CPB) induce ischemia-reperfusion and subsequent cellular injury with inflammatory reaction. Clinical and experimental studies suggest that recombinant human erythropoietin (EPO) independently of its erythropoietic effect may be used as a cytoprotective agent against ischemic injury. We tested the hypothesis that one large dose of EPO administered shortly before CPB prevents the elevation of cardiac and cerebral ischemic blood markers as well as the systemic inflammatory response induced by cardiac surgery with CBP through this randomized double-blind placebo-controlled pilot trial. ⋯ Compared with the placebo, EPO administration before CPB did not prevent an increase of all these markers following CPB. In conclusion, one large dose of EPO, given shortly before CPB, did not protect against cardiac and cerebral ischemia and inflammatory response occurring during CABG surgery with CPB. Although the long-term clinical implications remain unknown, the findings do not support use of EPO at this dose as a cytoprotective agent in patients undergoing cardiac surgery.
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Fundam Clin Pharmacol · Dec 2012
Randomized Controlled TrialSt John's wort greatly decreases the plasma concentrations of oral S-ketamine.
Ketamine is an intravenous anaesthetic and analgesic agent but it can also be used orally as an adjuvant in the treatment of chronic pain. This study investigated the effect of the herbal antidepressant St John's wort, an inducer of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of oral S-ketamine. In a randomized cross-over study with two phases, 12 healthy subjects were pretreated with oral St John's wort or placebo for 14 days. ⋯ There was a statistically significant linear correlation between the self-reported drug effect and C(max) of ketamine (r = 0.55; P < 0.01). St John's wort greatly decreased the exposure to oral S-ketamine in healthy volunteers. Although this decrease was not associated with significant changes in the analgesic or behavioural effects of ketamine in the present study, usual doses of S-ketamine may become ineffective if used concomitantly with St John's wort.
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Fundam Clin Pharmacol · Jun 2012
Randomized Controlled TrialTropisetron and paracetamol association in post-operative patients.
Studies in animals and in healthy volunteers have demonstrated the central serotonergic analgesic mechanism of action of paracetamol involving the inhibition of this analgesia by tropisetron, a 5-HT3 antagonist. This randomized, double-blind, controlled study aims at studying this interaction in post-operative patients after ear surgery. ⋯ The difference between the sums of numerical scales of both groups [9 ± 10 (T) vs. 6 ± 7 (c)] is not significant, but the tropisetron group displays higher pain scores despite additional rescue analgesia. The limits of this trial call for a much larger study to investigate further this pharmacodynamic interaction.
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Fundam Clin Pharmacol · Aug 2010
Randomized Controlled TrialThe antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes.
The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P = 0.007). ⋯ The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.