Sirolimus contd

Editors' Notes:

To minimize the variability of blood concentrations, sirolimus should be taken consistently in relation to time of administration with or without cyclosporine and/or food.

Sirolimus solution - For simultaneous administration, the mean Cmax and AUC of sirolimus were increased by 116% and 230%, respectively, relative to administration of sirolimus alone. However, when given 4 hours after NeoralĀ® Soft Gelatin Capsules (cyclosporine capsules [MODIFIED]) administration, sirolimus Cmax and AUC were increased by 37% and 80%, respectively, comparedto sirolimus alone. Cyclosporine clearance was reduced only after multiple-dose administration over 6 months.

Sirolimus tablets - For simultaneous administration, mean Cmax and AUC were increased by 512% and 148%, respectively, relative to administration of sirolimus alone. However, when given 4 hours after cyclosporine administration, sirolimus Cmax and AUC were both increased by only 33% compared with administration of sirolimus alone.

Sirolimus is an excellent immunosuppressant without apparent nephrotoxicity. The major problems with clinical use are delayed wound healing in some recipients and hyperlipidemia.

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