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• W2019854995 abstract "To compare the pharmacokinetics of mycophenolic acid when given with either ciclosporin or sirolimus, and investigate in vitro the potential effect of ciclosporin, sirolimus, tacrolimus and everolimus on mycophenolic acid metabolism.In renal transplant patients given mycophenolate mofetil in combination with ciclosporin (n = 19) or sirolimus (n = 12), concentration-time profiles of mycophenolic acid, mycophenolic-acid-phenyl-glucuronide, mycophenolic-acid-acyl-glucuronide and mycophenolic-acid-phenyl-glucoside were determined at one month post-transplant. The effect of immunosuppressive drugs on mycophenolic acid glucuronidation and glycosylation was investigated in vitro using human liver microsomes.The mean mycophenolic acid AUC(0-9 h) in the sirolimus group was 44.9 mg h(-1) L(-1) (95% CI: 34.7-55.1), vs. 30.5 mg h(-1) L(-1) (95% CI: 25.4-35.6) in the ciclosporin group, corresponding to 1.5-fold dose-normalized difference (95% CI: 1.1-1.9; P < 0.05). In addition, the metabolite/mycophenolic acid AUC(0-9 h) ratios were significantly higher in patients cotreated with ciclosporin than with sirolimus, giving values of 1.8-fold (95% CI: 1.3-2.3; P = 0.0009), 2.6-fold (95% CI: 2.0-3.3; P < 0.0001) and 4.3-fold (95% CI: 2.6-6.0; P = 0.0016) for mycophenolic-acid-phenyl-glucuronide, mycophenolic-acid-acyl-glucuronide and mycophenolic-acid-phenyl-glucoside, respectively. In vitro, none of the immunosuppressive drugs tested inhibited mycophenolic acid metabolism.Patients taking mycophenolate mofetil and sirolimus experience a higher exposure to mycophenolic acid and a lower exposure to mycophenolic acid metabolites than those being treated with mycophenolate mofetil and ciclosporin. This interaction is probably not caused by inhibition of mycophenolic acid glucuronidation or glycosylation, but is more likely to be due to the influence of ciclosporin on the excretion of mycophenolic acid metabolites into bile." @default.
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• W2019854995 date "2006-02-27" @default.
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• W2019854995 title "A comparison of the effect of ciclosporin and sirolimus on the pharmokinetics of mycophenolate in renal transplant patients" @default.
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• W2019854995 doi "https://doi.org/10.1111/j.1365-2125.2006.02509.x" @default.
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