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Achieving a physiol...
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Johannsson, Gudmundur,1960Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
(författare)
Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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Oxford University Press (OUP),2016
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/239458
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https://gup.ub.gu.se/publication/239458URI
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https://doi.org/10.1530/eje-15-1212DOI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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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.
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Lennernas, H.
(författare)
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Marelli, C.
(författare)
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Rockich, K.
(författare)
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Skrtic, Stanko,1970Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xskrst
(författare)
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Göteborgs universitetInstitutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:European Journal of Endocrinology: Oxford University Press (OUP)175:1, s. 85-930804-46431479-683X
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