Two four-treatment crossover bioavailability studies were performed in panels of 12 adult male volunteers with eight different commercial prednisone tablets. Plasma samples from the first study were assayed by radioimmunoassay for both prednisone and prednisolone. Plasma samples from the second study were assayed for prednisolone only. Statistical analyses of the data showed significant differences in the rate of appearance of prednisolone in plasma, but not in the amount converted to prednisolone. Some observations are made on the relationships between prednisone and prednisolone concentrations in plasma following oral ~lministration of prednisone.KEY WORDS: prednisone bioavailability; elimination half-lives of prednisone and prednisolone; prednisone and prednisolone plasma levels following prednisone.
INTRODUCTIONWith the development of radioimmunoassays for prednisone (1) and its metabolite, prednisolone (2), it is now possible to measure the plasma levels of these steroids following the oral administration of a single, low dose of prednisone. The early observations, of Campagna et al. Sullivan, Hallmark, Sakmar; Weidler, Earhart, and Wagner reported data on some prednisone tablets. One of these (6) reported results of our first prednisone study.It is well documented that prednisone is metabolized to prednisolone (7-9), which is assumed to be its active form. However, in most of these studies the metabolites of prednisolone have been isolated only from urine, or plasma levels of prednisolone have been measured following high doses of prednisone. In only one unpublished study of DiSanto et al. has the determination of both prednisone and prednisolone in plasma been undertaken.This article reports the results of two four-treatment crossover studies with commercially available prednisone tablets. In the second prednisone study both prednisone and prednisolone plasma levels were measured, while in the third prednisone study only prednisolone was measured in plasma. All tablets utilized in the studies were purchased on the open market by the Food and Drug Administration.
EXPERIMENTAL
In Vitro StudiesDissolution testing was performed in the laboratories of the Food and Drug Administration according to the specifications of the USP XVIII. Results of dissolution rate tests on the same tablets by another method will be reported in a subsequent publication.
SubjectsTwelve adult male volunteers between the ages of 21 and 32 years, weighing between 60.3 and 82.6 kg and in good health, were selected for each study. Six of the subjects participated in both studies. Each subject received a medical history, physical examination, and blood and urine analysis including plasma 17-OHCS.All subjects selected received no barbiturates or other enzyme-inducing agents for a period of 30 days preceding the study until its completion. They received no other medication or alcoholic beverages for a period beginning 7 days preceding the study until completion of the study. The subjects were assigned numbers which were ordered according t...