Pharmacokinetics and Oral Bioavailability of Hydrocortisone

Derendorf, Hartmut; Möllmann, H; Barth, Jürgen; Möllmann, Carsten; Tunn, Sabine; Krieg, Michael

doi:10.1002/j.1552-4604.1991.tb01906.x

Cited by 145 publications

(112 citation statements)

References 6 publications

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“…Another possible factor that may account for this wide variation is that the intravenous dose of hydrocortisone used in the latter study (50 mg) was much higher than the dose used in the study conducted by Derendorf et al (1991) (20 mg) as well as in the present study (15 mg/m 2 ). Our observations are consistent with those of Derendorf et al (1991) who estimated the absolute bioavailability of hydrocortisone to be 95·9% (.. : 19·6).…”

Section: Discussionsupporting

confidence: 92%

“…The pharmacokinetic parameters determined following intravenous administration of hydrocortisone sodium succinate (Solu-Cortef, Pharmacia & Upjohn) in the present study are consistent with those previously reported after oral and intravenous administration of 20 mg hydrocortisone (Hoechst) (Derendorf et al 1991). The latter study was performed in healthy adult volunteers following suppression of the HPA axis by dexamethasone tablets given at 2200 h one day prior to the study.…”

Section: Discussionsupporting

confidence: 89%

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Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Charmandari¹,

Johnston²,

Brook³

et al. 2001

Journal of Endocrinology

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The management of congenital adrenal hyperplasia due to 21-hydroxylase (CYP21) deficiency requires glucocorticoid substitution with oral hydrocortisone given twice or thrice daily. In paediatric practice little is known of the bioavailability of oral hydrocortisone tablets used in these patients. The aim of this study was to assess the bioavailability of oral hydrocortisone and to evaluate current replacement therapy in the light of cortisol pharmacokinetic properties.We determined the bioavailability of hydrocortisone following oral and intravenous administration in sixteen (median age: 10·9 years, range: 6·0-18·4 years) adequately controlled CYP21 deficient patients. Serum total cortisol concentrations were measured at 20-min intervals for 24 h while patients were on oral substitution therapy, and at 10-min intervals for 6 h following an intravenous bolus of hydrocortisone in a dose of 15 mg/m 2 body surface area. The area under the serum total cortisol concentration versus time curve (AUC) following oral and intravenous administration of hydrocortisone was calculated using the trapezoid method. The bioavailability was estimated by dividing the corrected for dose AUC after oral hydrocortisone administration by the corrected for dose AUC after the intravenous hydrocortisone administration and was exemplified as a percentage. After oral administration of hydrocortisone in the morning, median serum total cortisol concentrations reached a peak of 729·5 nmol/l (range: 492-2520 nmol/l) at 1·2 h (range: 0·3-3·3 h) and declined monoexponentially thereafter to reach undetectable concentrations 7 h (range: 5-12 h) after administration. Following administration of the evening hydrocortisone dose, median peak cortisol concentration of 499 nmol/l (range: 333-736 nmol/l) was attained also at 1·2 h (range: 0·3-3·0 h) and subsequently declined gradually, reaching undetectable concentrations at 9 h (5-12 h) after administration of the oral dose. After the intravenous hydrocortisone bolus a median peak serum total cortisol concentration of 1930 nmol/l (range: 1124-2700 nmol/l) was observed at 10 min (range: 10-20 min). Serum cortisol concentrations fell rapidly and reached undetectable levels 6 h after the hydrocortisone bolus. The absolute bioavailability of oral hydrocortisone in the morning was 94·2% (90% confidence interval (CI): 82·8-105·5%) whereas the apparent bioavailability in the evening was estimated to be 128·0% (90% CI: 119·0-138·0%).We conclude that the bioavailability of oral hydrocortisone is high and may result in supraphysiological cortisol concentrations within 1-2 h after administration of high doses. The even higher bioavailability in the evening, estimated using as reference the data derived from the intravenous administration of hydrocortisone bolus in the morning, is likely to reflect a decrease in the hydrocortisone clearance in the evening. Decisions on the schedule and frequency of administration in patients with congenital adrenal hyperplasia should be based on the knowledge of the bioavailab...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Charmandari¹,

Johnston²,

Brook³

et al. 2001

Journal of Endocrinology

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“…This dosing regimen, based on that of Young et al (1995), was intended to produce a significant decrease in cortisol levels. In the hydrocortisone condition, 50 mg of hydrocortisone was given orally and was followed 1.5 h later by methamphetamine or placebo (Derendorf et al, 1991). In each of the three premedication conditions (metyrapone, hydrocortisone, or placebo), placebos were substituted for the other drug(s).…”

Section: Methodsmentioning

confidence: 99%

Altering Cortisol Level does not Change the Pleasurable Effects of Methamphetamine in Humans

Harris

Reus

Wolkowitz

et al. 2003

Neuropsychopharmacol

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Preclinical studies have linked corticosteroid secretion and levels with drug self-administration by animals. In a double-blind, cross-over study, subjective, physiological, and endocrine responses to intravenous doses of methamphetamine 0.5 mg/kg or placebo were assessed in eight methamphetamine-experienced subjects after three cortisol-modifying premedication conditions: augmenting cortisol level with oral hydrocortisone 50 mg, blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone 1500 mg orally, or no premedication. Although the pharmacologic manipulations produced the expected hormonal changes, subjective response to the methamphetamine showed few differences. Diminishing cortisol response by pharmacologic blockade did not alter the pleasurable effects of methamphetamine. Hydrocortisone did increase self-reported 'bad drug effect' and decreased craving after saline placebo relative to the period following methamphetamine. Metyrapone was associated with significant premature ventricular complexes in two subjects during methamphetamine administration and may not be safe for those who use methamphetamine.

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“…Newer estimates of the cortisol production rate (see above) indicate that 15-20 mg total daily HC is required. Unfortunately, HC has a short plasma half-life and patients taking this tablet wake with undetectable cortisol levels, thus achieving peak cortisol levels an hour after dosing (14,62). The pharmacokinetics of 20 mg HC has been studied after i.v.…”

Section: Different Regimens and Dosesmentioning

confidence: 99%

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

Debono

Ross²,

Newell‐Price

2009

European Journal of Endocrinology

113

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Patients with adrenal insufficiency need lifelong glucocorticoid replacement, but many suffer from poor quality of life, and overall there is increased mortality. Moreover, it appears that use of glucocorticoids at the higher end of the replacement dose range is associated with increased risk for cardiovascular and metabolic bone disease. These data highlight some of the inadequacies of current regimes.The cortisol production rate is estimated to be equivalent to 5.7-7.4 mg/m 2 per day, and a major difficulty for replacement regimes is the inability to match the distinct circadian rhythm of circulating cortisol levels, which are low at the time of sleep onset, rise between 0200 and 0400 h, peaking just after waking and then fall during the day. Another issue is that current dose equivalents of glucocorticoids used for replacement are based on anti-inflammatory potency, and few data exist as to doses needed for equivalent cardiovascular and bone effects. Weight-adjusted, thrice-daily dosing using hydrocortisone (HC) reduces glucocorticoid overexposure and represents the most refined regime for current oral therapy, but does not replicate the normal cortisol rhythm. Recently, proof-of-concept studies have shown that more physiological circadian glucocorticoid therapy using HC infusions and newly developed oral formulations of HC have the potential for better biochemical control in patients with adrenal insufficiency. Whether such physiological replacement will have an impact on the complications seen in patients with adrenal insufficiency will need to be analysed in future clinical trials.

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Pharmacokinetics and Oral Bioavailability of Hydrocortisone

Cited by 145 publications

References 6 publications

Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Altering Cortisol Level does not Change the Pleasurable Effects of Methamphetamine in Humans

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

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