Distribution and metabolism of prednisone in mice, dogs, and monkeys

El Dareer, S.M.; Struck, R.F.; White, V.M.; Mellett, L.B.; Hill, D.L.

Cancer Treatment Reports 61(7): 1279-1289


ISSN/ISBN: 0361-5960
PMID: 412589
Document Number: 402
A chromatographic procedure that allows measurement of the antitumor agent [3H]prednisone and [3H]prednisolone in biologic fluids and tissues was developed and used to determine some of the biochemical properties of prednisone and its distribution and metabolism in mice, dogs and monkeys. When prednisone was added to mouse serum in vitro at a concentration of 50 .mu.g/ml, approximately half of the drug became bound to serum proteins. Homogenates of mouse liver metabolized prednisone to prednisolone. Following i.p. or oral doses of prednisone to mice, serum levels of prednisone, prednisolone and other metabolites were maximum at 15 min. 20-Dihydroprednisolene was identified as a metabolite in several biologic samples. For dogs and monkeys given an i.v. dose of prednisone, disappearance from the serum was biphasic with apparent half-lives of 15 and 82 min and 33 and 78 min, respectively. The serum levels of prednisone and prednisolone in mice, dogs and monkeys were not increased beyond expected levels by simultaneous administration of i.v. doses of vincristine. The prednisone content of the kidneys, liver, intestine and bile of a monkey killed 30 min after an i.v. dose was higher than that in serum. Oral doses of prednisone were absorbed erratically by dogs and monkeys. Only small amounts of prednisone and prednisolone were excreted in the urine of dogs and monkeys given an i.v. or oral dose.

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Distribution and metabolism of prednisone in mice, dogs, and monkeys