Rosuvastatin exposure was significantly increased in transplant recipients on an antirejection regimen including cyclosporine. Cyclosporine inhibition of OATP-C-mediated rosuvastatin hepatic uptake may be the mechanism of the drug-drug interaction. Coadministration of rosuvastatin with cyclosporine needs to be undertaken with caution.

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Summary: Monoamine oxidase (MAO) as a source of hy drogen peroxide (H202) was evaluated during ischemia reperfusion in vivo in the rat brain. H202 production was assessed with and without inhibition of MAO during and after 15 min of ischemia. Metabolism of H202 by catalase during ischemia and reperfusion was measured in fore brain homogenates using aminotriazole (A TZ), an irre versible HzOz-dependent inhibitor of catalase. Catechol amine and glutathione concentrations in forebrain were measured with and without MAO inhibitors. During isch emia, forebrain blood flow was reduced to 8% of baseline and HzOz production decreased as measured at the mi croperoxisome. During reperfusion, a rapid increase in H20Z generation occurred within 5 min as measured by a threefold increase in oxidized glutathione (GSSG). The Abbreviations used: ANOVA, analysis of variance; ATZ, 3-amino-l,2,4-triazole; DTNB, 5,5' -dithiobis-(2-nitrobenzoic acid); GSH, reduced glutathione; GSSG, oxidized glutathione; MAO, monoamine oxidase; NEM, N-ethylmaleimide; ROS, re active oxygen species; SOD, superoxide dismutase. 125H202-dependent rates of A TZ inactivation of catalase be tween control and ischemia-reperfusion were similar, in dicating that H202 was more available to glutathione per oxidase than to catalase in this model. MAO inhibitors eliminated the biochemical indications of increased H20Z production and increased the catecholamine concentra tions. Mortality was 67% at 48 h after ischemia reperfusion, and there was no improvement in survival after inhibition of MAO. We conclude that MAO is an important source of H20Z generation early in brain reper fusion, but inhibition of the enzyme does not improve survival in this model despite ablating H202 production. Key Words: Reactive oxygen species-Central nervous system-Glutathione-Catalase-Catecholamines. To protect cells from damage by ROS, antioxi dant systems exist to detoxify these compounds.These systems include nonenzymatic "scavengers"