Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Mar 2008
Sex differences in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone in the Sprague-Dawley rat.
1. The pharmacokinetics and oxidative metabolism of oxycodone were investigated following intravenous and oral administration in male and female Sprague-Dawley (SD) rats. 2. High-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS) was used to quantify plasma concentrations of oxycodone and its oxidative metabolites noroxycodone and oxymorphone following administration of single bolus intravenous (5 mg/kg) and oral (10 mg/kg) doses of oxycodone. 3. ⋯ Sex differences were apparent in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone. Systemic exposure to oxycodone was greater in female compared with male SD rats, whereas systemic exposure to metabolically derived noroxycodone was higher in male than female SD rats. 7. Oral administration of oxycodone to the SD rat is a poor model of the human for the study of the pharmacodynamic effects of oxycodone.
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Clin. Exp. Pharmacol. Physiol. · Mar 2008
Alpha-lipoic acid protects against renal ischaemia-reperfusion injury in rats.
1. Oxygen free radicals are important components involved in the pathophysiological processes observed during ischaemia-reperfusion (I/R). The present study was designed to assess the possible protective effect of alpha-lipoic acid (ALA) on renal I/R injury. 2. ⋯ Conversely, ALA treatment reversed all these biochemical indices, as well as histopathological alterations induced by I/R. 5. In conclusion, these data suggest that ALA reverses I/R-induced oxidant responses and improves microscopic damage and renal function. Thus, it seems likely that ALA protects kidney tissues by inhibiting neutrophil infiltration, balancing the oxidant-anti-oxidant status and regulating the generation of inflammatory mediators.