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• W1992376246 abstract "Abstract The changes of physiological conditions in obesity could make the treatment with CyA more complicated and heterogeneous; in particular, the elevation of serum lipids and fatty liver have great potential to affect the biodistribution and metabolism of CyA. The aim of the present study is to investigate the effect of obesity on the pharmacokinetics of CyA in high-fat-fed rats (HF rats). After intravenous and intraduodenal administration to HF rats, AUC 0−∞ of CyA was significantly increased in comparison with that of controls (2.8- and 1.5-fold, respectively), and the distribution volume at steady state (Vd ss ) in HF rats was significantly decreased to 56%, possibly due to increased lipoprotein binding ratio of CyA. In contrast, t 1/2 did not show notable changes, despite the decrease of Vd ss in HF rats. The hepatic distribution of CyA in HF rats was significantly higher than that in controls. It was considered that, as a lipid complex, CyA uptake via the lipoprotein receptor into hepatocytes could increase in HF rats and counteract the decrease of Vd ss , resulting in comparable t 1/2 . It was noted that the oral bioavailability of CyA was significantly decreased to 54% in HF rats, whereas the metabolism in intestinal and hepatic microsomes indicated no notable difference in the first-pass effect of CyA. These results suggested that when switching from a CyA injectable formulation to an oral one in obese patients, the attenuation of oral bioavailability should be taken into account in a dose adjustment, even though its mechanism has been unclear and warrants further investigation." @default.
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• W1992376246 date "2011-07-01" @default.
• W1992376246 modified "2023-09-26" @default.
• W1992376246 title "Effects of obesity induced by high-fat diet on the pharmacokinetics of cyclosporine A in rats" @default.
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• W1992376246 doi "https://doi.org/10.1016/j.bionut.2011.06.007" @default.
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