Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomised trial of a novel hydrocortisone dual-release formulation
| العنوان: | Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomised trial of a novel hydrocortisone dual-release formulation |
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| المؤلفون: | Johansson, G., Nilsson, A. G., Bergthorsdottir, R., Burman, P., Dahlqvist, P., Ekman, Bertil, Engström, B. E, Olsson, T., Ragnarsson, O., Ryberg, M., Wahlberg, Jeanette, 1969, Biller, B. M. K., Monson, J. P., Stewart, P. M., Lennernäs, H., Skrtic, S. |
| المصدر: | Journal of Clinical Endocrinology and Metabolism. 97(2):473-481 |
| الوصف: | 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. |
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| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-110330 https://doi.org/10.1210/jc.2011-1926 |
| قاعدة البيانات: | SwePub |
| تدمد: | 0021972X 19457197 |
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| DOI: | 10.1210/jc.2011-1926 |