ECE2010 Poster Presentations Adrenal (66 abstracts)
Pharmacokinetic evidence for hydrococortisone under and over replacement in adrenal insufficiency
Frederic Castinetti 1 , Nicolas Simon 2 , Floriane Ouliac 1, , Nathalie Lesavre 4 , Thierry Brue 1 & Charles Oliver 1
1Department of Endocrinology, Timone Hospital, Marseille, France; 2Pharmacology Department, Faculty of Medicine, Marseille, France; 3Department of Endocrinology, North Hospital, Marseille, France; 4Clinical Investigation Centre, Marseille, France.
Aim and methods: Cortisol substitution in adrenal insufficiency (AI) is a matter of debate. We performed a pharmacokinetic analysis of plasma and salivary cortisol following oral hydrocortisone intake in patients with AI, and a pharmacokinetic modelling simulation. Fifty patients with primary (n=20) or secondary (n=30) AI were recruited. After 24-h plasma and salivary cortisol measurements under usual hydrocortisone treatment, a pharmacokinetic modelling with different simulated hydrocortisone dosing at different times of the day was performed.
Results: Thirteen different treatments regimens were observed: plasma and salivary cortisol levels were not in the normal range in the majority of patients. Pharmacokinetic modelling showed that there was a wide variability in cortisol concentrations whatever the scheme simulated, with the majority of patients under or over-replaced: the regimen with the higher proportion of simulated patients within the biological targets was 10+5+5 mg at 0730 h, 1200 and 1630 h respectively; however, even with this scheme, about 40% of patients would remain over or under-replaced.
Conclusions: Most patients are imperfectly treated. Our pharmacokinetic modelling showed that optimal substitution remains difficult with current tablets of hydrocortisone, whatever dose and time of administration used.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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