How is prednisone metabolized?
Prednisone is metabolized in the liver to the active form, prednisolone. This conversion is impaired in patients with significant liver disease, which is present if the patient has an elevated international normalized ratio (INR) that cannot be normalized with supplemental vitamin K. In those patients, prednisolone and not prednisone should be given. The prednisolone half-life is 2.1 to 3.5 hours. Therefore, prednisone effects may wane after five half-lives. For this reason, splitting the dose of high-dose prednisone to twice a day when treating severe disease manifestations will assure that therapeutic effects last for 24 hours. The maximum effect on lymphocytes by redistribution and genomic effects occurs at a single dose of 20 to 30 mg; therefore doses of 20 to 30 mg once a day is more immunosuppressive than a split dose regimen of 10 to 15 mg twice daily. At the tissue level, GCs are inactivated by 11-β hydroxysteroid dehydrogenase type 2 isoenzyme. This isoenzyme has various polymorphisms that determine how sensitive a person is to GCs and may help explain why some patients get more side effects than others.