Fundamental & clinical pharmacology
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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 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 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.