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- Johannsson, Gudmundur, et al.
(författare)
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Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone : a pharmacokinetic study
- 2016
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 175:1, s. 85-93
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
- Stewart, Paul M, et al.
(författare)
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Exploring Inpatient Hospitalizations and Morbidity in Patients With Adrenal Insufficiency.
- 2016
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 101:12, s. 4843-4850
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Tidskriftsartikel (refereegranskat)abstract
- Patients with adrenal insufficiency (AI) (primary AI [PAI], secondary AI due to a pituitary disorder [PIT] and congenital adrenal hyperplasia [CAH]) have reduced life expectancy; however, the underlying explanation remains unknown.To evaluate characteristics, comorbidities, and hospitalizations in AI patients.Retrospective observational.Using a United States-based national payer database comprising of more than 108 million members, strict inclusion criteria including diagnostic codes and steroid prescription records were used to identify 10 383 adults with AI; 1014 with PAI, 8818 with PIT, and 551 with CAH. Patients were matched 1:1 to controls, based on age (±5 y), gender, insurance, and region and followed for more than 12 months.None.Demographic variables, comorbidities (diabetes mellitus [DM] types 1 and 2, depression, anxiety, hyperlipidemia, hypertension) and hospitalization incidence.Compared with controls, patients with AI had higher odds of DM, hypertension, hyperlipidaemia, depression, and anxiety, ranging from an odds ratio (OR) of 1.51 for hyperlipidaemia in PAI to 3.85 for DM in CAH. Odds of having DM (OR, 3.85; 95% confidence interval, 2.52-5.90) or anxiety (OR, 2.99; 95% confidence interval, 2.02-4.42) compared with controls were highest in CAH, whereas depression was highest in PAI and PIT (OR, 2.40 and 2.55). ORs of hyperlipidaemia and hypertension (OR, 1.98 and 2.24) were highest in the PIT cohort. Inpatient admissions were more frequent in PAI (4.64:1; P < .0001) and PIT (4.00:1; P < .0001) than controls; infection was the most common cause for admission.Patients with AI carry a significant metabolic and psychiatric burden, with higher risk of comorbidities and hospital admissions than matched controls.
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