Circadian rhythm of serum cortisol after repeated inhalation of the new topical steroid ciclesonide.
The new inhalative glucocorticoid ciclesonide which is activated in lung to a more potent metabolite was hypothesized to have low risk for systemic and local side-effects in man. Therefore, a placebo-controlled, randomized, double-blind, four-period, change-over equivalence study in 12 healthy male volunteers (age 21-28 yr, body weight 62-90 kg) was conducted to assess the influence of three dosage regimens (800 microg in the morning, 800 microg in the evening, 400 microg twice daily for 7 d, metered inhalers) on the circadian time serum cortisol rhythm.


RESULTS
Serum cortisol showed the typical circadian rhythm. The geometric mean of the 24-h mesor (AUC((0-24 h))/24 h) was 7.22 microg/dl for placebo, 6.75 microg/dl for the 800 microg ciclesonide morning dose, 7.08 microg/dl for the 800 microg evening dose, and 6.75 microg/dl for 400 microg ciclesonide inhaled twice daily. Because there was also no influence on cortisol amplitude and acrophase (time of maximum), the profiles after ciclesonide were equivalent to the placebo control. The small differences were considered not to be of clinical significance. In conclusion, inhaled ciclesonide in daily doses of 800 microg for 7 d is without clinically relevant effects on the hypothalamic-pituitary-adrenal axis independent of the time of administration.
Weinbrenner
Anita
A
Department of Clinical Pharmacology, Ernst Moritz Arndt University, Greifswald 17487, Germany.
Hüneke
Dagny
D
Zschiesche
Michael
M
Engel
Georg
G
Timmer
Wolfgang
W
Steinijans
Volker W
VW
Bethke
Thomas
T
Wurst
Wilhelm
W
Drollmann
Anton
A
Kaatz
Hans Joachim
HJ
Siegmund
Werner
W
D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D011282:Pregnenediones / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology
D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C120481:ciclesonide; D006854:Hydrocortisone