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Improving glucocort...
Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study.
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- Johannsson, Gudmundur, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Bergthorsdottir, Ragnhildur, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Nilsson, Anna G, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Lennernäs, Hans (author)
- Uppsala universitet,Institutionen för farmaci
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- Hedner, Thomas, 1949 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för klinisk prövning och entreprenörskap,Institute of Medicine, Department of Clinical Trials and Entrepreneurship
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- Skrtic, Stanko, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för klinisk prövning och entreprenörskap,Institute of Medicine, Department of Clinical Trials and Entrepreneurship
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 161:1, s. 119-30
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Abstract
Subject headings
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- BACKGROUND: Endogenous plasma cortisol levels have a well-defined circadian rhythm. The aim of this project is to develop a once daily oral dual-release formulation for cortisol replacement therapy that mimics the diurnal variation in the plasma cortisol profile. OBJECTIVE: To determine single-dose plasma pharmacokinetics and dose-proportionality of oral 5 and 20 mg dual-release hydrocortisone tablets in healthy volunteers. In addition, the effect of food intake was investigated for the 20 mg dose. DESIGN: A randomised, controlled, two-way cross-over, double-blind, phase I study of oral hydrocortisone (modified (dual) release; 5 and 20 mg) with an open food-interaction arm. METHODS: The single dose pharmacokinetic studies were performed with betamethasone suppression. The two first study days were blinded and randomised between morning administration of 5 and 20 mg tablet in a fasting state. The third day was open with a 20 mg tablet taken 30 min after a high-calorie, high-fat meal. The plasma samples were assayed using both a validated LC-MS/MS and an immunoassay. The plasma pharmacokinetic variables were calculated using non-compartmental data analysis. RESULTS: The time to reach a clinically significant plasma concentration of cortisol (>200 nmol/l) was within 20 min and a mean peak of 431 (s.d. 126) nmol/l was obtained within 50 min after administration of the 20 mg tablet. Plasma cortisol levels remained above 200 nmol/l for around 6 h thereafter and all plasma concentrations 18-24 h after intake were below 50 nmol/l. In the fed state the time to reach 200 nmol/l was delayed by 28 and 9 min based on LC-MS/MS and immunoassay, respectively. The 5 and 20 mg tablets produced an increase in plasma exposure of cortisol that was not fully dose proportional. CONCLUSION: The dual release hydrocortisone tablet with once-daily administration produced a diurnal plasma cortisol profile mimicking the physiological serum cortisol profile.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Administration
- Oral
- Adolescent
- Adult
- Aged
- Anti-Inflammatory Agents
- administration & dosage
- blood
- pharmacokinetics
- Circadian Rhythm
- Cross-Over Studies
- Eating
- Female
- Hormone Replacement Therapy
- methods
- Humans
- Hydrocortisone
- administration & dosage
- blood
- pharmacokinetics
- Male
- Middle Aged
- Tablets
- Young Adult
- MEDICINE
- PHARMACY
Publication and Content Type
- ref (subject category)
- art (subject category)
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