ISSN:
1432-1041
Keywords:
fluocortolone
;
cortisol
;
alternate day therapy
;
plasma cortisol ACTH
;
plasma level
;
healthy volunteers
;
circadian rhythm
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The pharmacokinetics of fluocortolone and its effect on the circadian rhythm of plasma cortisol and ACTH have been studied during different schedules of oral administration. Groups of 6 healthy male adults were given a single daily dose of fluocortolone 5, 10 and 20 mg, and another group received 20 mg every second day. Administration to all groups was continued for 8 days. Pharmacokinetic parameters of fluocortolone (half lives of absorption- t1/2a and elimination t1/2e, volume of distribution V and oral clearance (CL/f) were independent of the duration of treatment and dose. Areas under the plasma level curves, AUC and Cmax values increased in proportion to the dose, indicating dose linearity of fluocortolone pharmacokinetics. A normal morning cortisol peak occurred during all treatment schedules, which indicates that circadian cortisol secretion was not seriously affected by the glucocorticoid treatment. On the other hand, when the level of circulating fluocortolone was high the 12.00 a.m. and 4.00 p.m. cortisol levels were diminished compared to the pre and posttreatment values. There was no definite correlation between the ACTH and cortisol levels, either on treatment or on control days. ACTH levels were suppressed by daily treatment with the 20 mg dose. Thus, even during administration of a high dose of a glucocorticoid, the circadian secretion of cortisol can be preserved if the treatment is adjusted according to the half-life of the drug.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00609249
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