Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Marelli C.) > Achieving a physiol...

Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study

Johannsson, Gudmundur, 1960 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition

Lennernas, H. (author)

Marelli, C. (author)

Rockich, K. (author)

Skrtic, Stanko, 1970 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition

show less...

(creator_code:org_t)

Oxford University Press (OUP), 2016
2016
English.
In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 175:1, s. 85-93

Related links:: https://eje.bioscien...; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Objective: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy was developed to provide a cortisol exposure-time profile that closely resembles the physiological cortisol profile. This study aimed to characterize single-dose pharmacokinetics (PK) of DR-HC 5-20 mg and assess intrasubject variability. Methods: Thirty-one healthy Japanese or non-Hispanic Caucasian volunteers aged 20-55 years participated in this randomized, open-label, PK study. Single doses of DR-HC 5, 15 (3 x 5), and 20 mg were administered orally after an overnight fast and suppression of endogenous cortisol secretion. After estimating the endogenous cortisol profile, PK of DR-HC over 24 h were evaluated to assess dose proportionality and impact of ethnicity. Plasma cortisol concentrations were analyzed using liquid chromatography-tandem mass spectrometry. PK parameters were calculated from individual cortisol concentration-time profiles. Results: DR-HC 20 mg provided higher than endogenous cortisol plasma concentrations 0-4 h post-dose but similar concentrations later in the profile. Cortisol concentrations and PK exposure parameters increased with increasing doses. Mean maximal serum concentration (C-max) was 82.0 and 178.1 ng/mL, while mean area under the concentration-time curve (AUC)(0-infinity) was 562.8 and 1180.8 h x ng/mL with DR-HC 5 and 20 mg respectively. Within-subject PK variability was low (<15%) for DR-HC 20 mg. All exposure PK parameters were less than dose proportional (slope < 1). PK differences between ethnicities were explained by body weight differences. Conclusions: DR-HC replacement resembles the daily normal cortisol profile. Within-subject day-to-day PK variability was low, underpinning the safety of DR-HC for replacement therapy. DR-HC PK were less than dose proportional - an important consideration when managing intercurrent illness in patients with adrenal insufficiency.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

glucocorticoid replacement therapy
adrenal insufficiency
premature
mortality
hypopituitarism
secretion
sleep
diagnosis
outcomes
pattern
stress

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

European Journal of Endocrinology (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Johannsson, Gudm ...; Lennernas, H.; Marelli, C.; Rockich, K.; Skrtic, Stanko, ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

Articles in the publication: European Journal ...

By the university: University of Gothenburg

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se