Replacement therapy of oral hydrocortisone in adrenal insufficiency: the influence of gastrointestinal factors

  title={Replacement therapy of oral hydrocortisone in adrenal insufficiency: the influence of gastrointestinal factors},
  author={Hans Lennern{\"a}s and Stanko Skrtic and Gudmundur Johannsson},
  journal={Expert Opinion on Drug Metabolism \& Toxicology},
  pages={749 - 758}
Background: Replacing glucocorticoids in primary adrenal insufficiency (AI) or Addison's disease (AD) is today based on oral replacement therapy with hydrocortisone in a conventional immediate-release tablet. It is recognised that physiological gastrointestinal factors may have a strong influence on the plasma concentration-time profile of hydrocortisone. Hydrocortisone has a sufficiently high permeability in both the small and large intestine, but in vivo dissolution from the available oral… 

Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study.

The dual release hydrocortisone tablet with once-daily administration produced a diurnal plasma cortisol profile mimicking the physiological serum cortisol profile.

Improving glucocorticoid replacement in patients with adrenal insufficiency

Data is reported from a clinical intervention study using a newly developed drug, a dual-release oral HC (DR-HC) formulation for glucocorticoid replacement, which has an outer layer of immediate- release HC allowing a peak serum cortisol concentration in the morning after an oral administration in the fasting state and an inner core with modified-release HC that mimics the serum cortisol profile throughout the day and evening.

Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone

The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy, with increased 11β-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency.

Predicting Cortisol Exposure from Paediatric Hydrocortisone Formulation Using a Semi-Mechanistic Pharmacokinetic Model Established in Healthy Adults

A semi-mechanistic population pharmacokinetic model based on studies in healthy adult volunteers is established to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency and captures the complex pharmacokinetics of hydrocordisone in a simplified but comprehensive framework.

An oral multiparticulate, modified‐release, hydrocortisone replacement therapy that provides physiological cortisol exposure

It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency with modified‐release technology, so new formulations using multiparticulate technology are developed.

Digestive symptoms in daily life of chronic adrenal insufficiency patients are similar to irritable bowel syndrome symptoms

Assessment and management of digestive symptoms should be considered a priority for physicians treating patients with CAI and similar to symptoms of irritable bowel syndrome in 30% of CAI patients.

Signal Transduction of Steroidogenic Hormones to the Adrenal and Gonadal Mitochondria and the Possibilities for Combating Lipoid Congenital Adrenal Hyperplasia

A complete understanding of the workings of the signal transduction machinery in steroidogenic cells may allow future plans to combat LCAH by using gene therapy to restore appropriate activity to StAR gene products.

Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship

Available data provides support for existing theoretical frameworks which postulate that in AD and other neuroendocrine, neurological, or psychiatric disorders, disrupted sleep is an important biological mechanism that underlies, at least partially, the memory impairments that patients frequently report experiencing.

In Vitro Evaluation of Cocoa Pod Husk Pectin as a Carrier for Chronodelivery of Hydrocortisone Intended for Adrenal Insufficiency

The optimized CPH pectin-based hydrocortisone matrix tablets exhibited a lag phase of ~6 h followed by accelerated drug release in the colonic region and have potential to control night time cortisol levels in patients with adrenal insufficiency.



Continuous subcutaneous hydrocortisone infusion in Addison's disease.

A daily dose of approximately 10 mg/m(2) body surface area/day restores the circadian variation and normal levels of salivary cortisol in most patients, which is close to the estimated daily requirement.

Why is the management of glucocorticoid deficiency still controversial: a review of the literature

The available evidence suggests that most patients may safely be treated with a low dose of glucocorticoid (e.g. 15 mg hydrocortisone daily) in two or three divided doses, with education about the appropriate action to take in the event of intercurrent illnesses.

The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients.

Heq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile, and CA replacement may have metabolic advantages compared with other GCs.

Effect of dose size on the pharmacokinetics of intravenous hydrocortisone during endogenous hydrocortisone suppression

Changes in the pharmacokinetic parameters following oral hydrocortisone at high doses may be related to drug concentrationdependent changes in the binding of hydroc Cortisone to plasma proteins.

Non‐physiological levels of circulating cortisol in growth hormone‐treated hypopituitary adults after conventional cortisone substitution

Conventional cortisone substitution with a twice‐daily replacement regimen in hypopituitary adults results in abnormal circulating cortisol profiles with low or non‐measurable morning values and variable individual peaks, suggesting that the present dosing schemes have to be improved and that cortis one substitution should be individualized.

Effect of dose size on the pharmacokinetics of oral hydrocortisone suspension.

The pharmacokinetics of hydrocortisone were examined following single doses of 5-, 10-, 20-, and 40-mg hydrocortisone suspensions to healthy male volunteers. Endogenous hydrocortisone was suppressed

Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids

Simulations with a pharmacokinetic/pharmacodynamic model using T helper cell counts and endogenous Cortisol as biomarkers for the effects of methylprednisolone suggest that the clinical efficacy of low-dose glucocorticoid regimens might be increased with twice-daily glucocORTicoid administration.

Glucocorticoid replacement therapy in patients with Addison’s disease

The controversial glucocorticoid replacement therapy in patients with Addison’s disease is discussed, and a good review of literature and suggested guidelines for appropriate treatment of this disease are provided.

Oral hydrocortisone pharmacokinetics: a comparison of fluorescence and ultraviolet high-pressure liquid chromatographic assays for hydrocortisone in plasma.

Within the dosage range studied, plasma levels of hydrocortisone were related, but not directly proportional, to dose size, and this apparent lack of proportionality may be due to reduced drug availability or altered distribution with increasing dose.

Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia

The potential of circadian delivery of hydrocortisone as proof of concept for therapy delivered in modified‐release tablet formulation for adrenal insufficiency is explored.