Biomaterial Database

Pharmacokinetic/pharmacodynamic modeling of cortisol suppression after oral administration of fluocortolone. 1996

S Rohatagi, and U Täuber, and K Richter, and H Derendorf

Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.

Fluocortolone is a potent corticosteroid used orally for the treatment of rheumatic diseases, asthma, and immunosuppression. A clinical study of nine healthy volunteers was conducted to determine the pharmacokinetics and cortisol suppression after administration of single oral doses of 20 mg, 50 mg, and 100 mg of fluocortolone. Blood samples were collected at 8:00 AM, 12:00 PM, and 4:00 PM on the day before treatment, and 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 28, 32, 48, 52, and 56 hours after administration of the drug. Concentrations of fluocortolone and cortisol were measured in plasma by a reversed phase high-performance liquid chromatography system. Cortisol suppression was chosen as the pharmacodynamic parameter. Total concentrations were converted into unbound concentrations using a two-protein, one-ligand equation. The unbound concentrations were fitted using a one-compartment body model equation with first-order absorption. A linear release-rate model was used to characterize the cortisol data. The data were fitted using a common E50 value of 0.95 +/- 0.22 ng/mL for the mean data. The value of E50 was in close agreement with the prediction based on relative glucocorticoid receptor affinity.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D005448	Fluocortolone	A glucocorticoid with anti-inflammatory activity used topically for various skin disorders.	Fluocortolone Caproate,Fluocortolone Pivalate,Ultralan,Caproate, Fluocortolone,Pivalate, Fluocortolone
D005938	Glucocorticoids	A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.	Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006854	Hydrocortisone	The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.	Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D018592	Cross-Over Studies	Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)	Cross-Over Design,Cross-Over Trials,Crossover Design,Crossover Studies,Crossover Trials,Cross Over Design,Cross Over Studies,Cross Over Trials,Cross-Over Designs,Cross-Over Study,Crossover Designs,Crossover Study,Design, Cross-Over,Design, Crossover,Designs, Cross-Over,Designs, Crossover,Studies, Cross-Over,Studies, Crossover,Study, Cross-Over,Study, Crossover,Trial, Cross-Over,Trial, Crossover,Trials, Cross-Over,Trials, Crossover
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In