Improved Cortisol Exposure-Time Profile and Outcome in Patients with Adrenal Insufficiency: A Prospective Randomized Trial of a Novel Hydrocortisone Dual-Release Formulation.
(2011) In The Journal of clinical endocrinology and metabolism 97(2). p.473-481- Abstract
- Context:Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.Objective:The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.Design and Setting:We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.Patients:The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).Intervention:The same daily dose of hydrocortisone was... (More)
- Context:Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.Objective:The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.Design and Setting:We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.Patients:The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).Intervention:The same daily dose of hydrocortisone was administered as OD dual-release or TID.Main Outcome Measure:We evaluated cortisol pharmacokinetics.Results:Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).Conclusion:The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM. (Less)
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https://lup.lub.lu.se/record/2220387
- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of clinical endocrinology and metabolism
- volume
- 97
- issue
- 2
- pages
- 473 - 481
- publisher
- Oxford University Press
- external identifiers
-
- wos:000301226800043
- pmid:22112807
- scopus:84856451930
- ISSN
- 1945-7197
- DOI
- 10.1210/jc.2011-1926
- language
- English
- LU publication?
- yes
- id
- 574a1496-7319-4bb0-9a5a-102587383350 (old id 2220387)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22112807?dopt=Abstract
- date added to LUP
- 2016-04-01 13:22:33
- date last changed
- 2024-05-09 06:09:23
@article{574a1496-7319-4bb0-9a5a-102587383350,
abstract = {{Context:Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.Objective:The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.Design and Setting:We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.Patients:The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).Intervention:The same daily dose of hydrocortisone was administered as OD dual-release or TID.Main Outcome Measure:We evaluated cortisol pharmacokinetics.Results:Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).Conclusion:The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.}},
author = {{Johannsson, G and Nilsson, A G and Bergthorsdottir, R and Burman, Pia and Dahlqvist, P and Ekman, B and Engström, B E and Olsson, T and Ragnarsson, O and Ryberg, M and Wahlberg, J and Biller, B M K and Monson, J P and Stewart, P M and Lennernäs, H and Skrtic, S}},
issn = {{1945-7197}},
language = {{eng}},
number = {{2}},
pages = {{473--481}},
publisher = {{Oxford University Press}},
series = {{The Journal of clinical endocrinology and metabolism}},
title = {{Improved Cortisol Exposure-Time Profile and Outcome in Patients with Adrenal Insufficiency: A Prospective Randomized Trial of a Novel Hydrocortisone Dual-Release Formulation.}},
url = {{https://lup.lub.lu.se/search/files/3332797/2342620.pdf}},
doi = {{10.1210/jc.2011-1926}},
volume = {{97}},
year = {{2011}},
}