Estimation of the inter- and intrasubject variability of the diurnal serum cortisol rhythm in healthy male subjects to evaluate the biomarker potential for drug target engagement

2015 ◽  
Vol 53 (03) ◽  
pp. 199-205
Author(s):  
Fanni Natanegara ◽  
Adrienne Tran ◽  
Stephen Lowe ◽  
Lai San Tham ◽  
Christopher Chen
Keyword(s):  
Drug Target ◽  
Serum Cortisol ◽  
Target Engagement ◽  
Healthy Male ◽  
Intrasubject Variability ◽  
Male Subjects

scholarly journals The endotoxin-induced increase of cytokines is followed by an increase of cortisol relative to dehydroepiandrosterone (DHEA) in healthy male subjects

2002 ◽  
Vol 175 (2) ◽  
pp. 467-474 ◽  
Author(s):  
RH Straub ◽  
A Schuld ◽  
J Mullington ◽  
M Haack ◽  
J Scholmerich ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Time Course ◽  
Inflammatory Diseases ◽  
Serum Cortisol ◽  
Strong Increase ◽  
Healthy Male ◽  
Chronic Inflammatory Diseases ◽  
T Helper Lymphocyte ◽  
Cortisol Levels ◽  
Male Subjects

Dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) inhibit T-helper lymphocyte type 2 immune reactions and exert anti-inflammatory effects in some chronic inflammatory diseases. Both DHEA and, in particular, DHEAS levels are dramatically decreased in chronic inflammatory diseases whereas cortisol levels remain stable or are elevated. However, the time course of cortisol relative to DHEA production is not known. We tested whether administration of endotoxin to healthy male subjects can induce an early predominance of cortisol relative to DHEA and DHEAS. It is demonstrated that endotoxin induces a dose-dependent increase of cortisol in relation to DHEA (no effect at 0.2 ng endotoxin/kg body weight (b.w.), clear effect at 0.4 and 0.8 ng/kg b.w., p<0.05) and DHEAS (tested at 0.4 ng/kg b.w., P=0.014). The increase of cortisol relative to DHEA appears 4 h after endotoxin injection and 2 h after a strong increase of interleukin (IL)-6 relative to tumour necrosis factor (TNF). In addition, an increase of cortisol relative to 17OH-progesterone was observed. The ratio of serum IL-6/TNF was positively correlated with the ratio of serum cortisol/DHEA (R(Rank)=0.472, P=0.041) and serum cortisol/17OH-progesterone (R(Rank)=0.514, P=0.048). In conclusion, dissociation of cortisol relative to DHEA, DHEAS or 17OH-progesterone appears very early during a systemic inflammatory response which is associated with an increase of IL-6 relative to TNF. As in chronic inflammatory diseases, during an acute inflammatory response with endotoxin, these physiological hormone changes are probably necessary to achieve adequate cortisol levels at the expense of adrenal androgens.

884: Phase I, Double-Blind, Placebo-Controlled Study in Healthy Male Subjects to Investigate the Safety, Tolerability, and Pharmacokinetics of DA-8159

2004 ◽  
Vol 171 (4S) ◽  
pp. 234-234 ◽  
Author(s):  
Harin Padma-Nathan ◽  
Jae Seung Pacik ◽  
Byoung Ok Ahn ◽  
Kyung Koo Kang ◽  
Mi Young Bahng ◽  
...  
Keyword(s):  
Phase I ◽  
Controlled Study ◽  
Healthy Male ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Male Subjects
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