Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 22 P13

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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