Prednisone ADME

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R-HSA-9757110
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Homo sapiens
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5/5
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Prednisone (PREDN) is a prodrug of prednisolone (PREDL), and is rapidly absorbed. To achieve high uptake of the near water-insoluble molecule the highest dose 50 mg has to be dissolved in 250 ml water. Its conversion to the highly active prednisolone (PREDL) in liver cells is reversible but represents the favored reaction direction (Pickup, 1979).
Prednisone and prednisolone are considered to be fully therapeutically equivalent. The theoretical advantage of avoiding high GI concentrations of prednisone by administering prednisolone directly has never been shown to be clinically relevant (Vogt et al, 2007).
Only 2–5% of a given dose of prednisone is excreted unchanged in urine. After hydrogenation to prednisolone at least 20 metabolites and their conjugates are formed and excreted. The main metabolites both after systemic and topical use are 20alpha- and 20beta-dihydro-prednisone, as well as 20alpha- and 20beta-dihydro-prednisolone (20AH-PREDN, 20BH-PREDN, 20AH-PREDL, 20BH-PREDL), in addition to the 6beta-hydroxy compounds 6B-OH-PREDN and 6B-OH-PREDL (Matabosch et al, 2015; Mazzarino et al, 2019). Hydrogenation of PREDN and dehydrogenation of PREDL are complementary reactions that are dominant in different cell types. While liver and fat cells convert PREDN to PREDL, colon and kidney cells partly convert PREDL back to PREDN (Jamieson et al, 1995; Ricketts et al, 1998; Diederichs et al, 2002). We have depicted this equilibrium by showing example reactions in hepatocytes and kidney cells in the diagram.
Literature References
PubMed ID Title Journal Year
7588203 11 beta-hydroxysteroid dehydrogenase is an exclusive 11 beta- reductase in primary cultures of rat hepatocytes: effect of physicochemical and hormonal manipulations

Edwards, CR, Jamieson, PM, Chapman, KE, Seckl, JR

Endocrinology 1995
31701669 Urinary excretion profile of prednisone and prednisolone after different administration routes

Piantadosi, C, Comunità, F, Mazzarino, M, de la Torre, X, Botrè, F

Drug Test Anal 2019
25800201 Detection and characterization of prednisolone metabolites in human urine by LC-MS/MS

Pozo, OJ, Papaseit, E, Segura, J, Ventura, R, Pérez-Mañá, C, Matabosch, X

J Mass Spectrom 2015
9543163 Immunohistochemical localization of type 1 11beta-hydroxysteroid dehydrogenase in human tissues

Stewart, PM, Verhaeg, JM, Howie, AJ, Bujalska, I, Rainey, WE, Ricketts, ML

J Clin Endocrinol Metab 1998
12466373 11beta-hydroxysteroid dehydrogenase types 1 and 2: an important pharmacokinetic determinant for the activity of synthetic mineralo- and glucocorticoids

Seidelmann, D, Rochel, M, Oelkers, W, Quinkler, M, Esperling, P, Bumke-Vogt, C, Bähr, V, Burkhardt, P, Diederich, S, Eigendorff, E

J Clin Endocrinol Metab 2002
378499 Clinical pharmacokinetics of prednisone and prednisolone

Pickup, ME

Clin Pharmacokinet 1979
17387693 Biowaiver monographs for immediate release solid oral dosage forms: prednisone

Derendorf, H, Midha, KK, Stavchansky, S, Kramer, J, Junginger, HE, Vogt, M, Dressman, JB, Barends, DM, Shah, VP

J Pharm Sci 2007
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