Studies on an Intermittent Corticosteroid Dosage Regimen

Harter, John G.; Reddy, William J.; Thorn, George W.

doi:10.1056/nejm196309192691201

Cited by 339 publications

(100 citation statements)

References 14 publications

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“…The alternate-day glucocorticoid therapy with a single dose in the morning of every second day was first proposed by Harter et al (1963), and many authors have found that such a regimen diminishes side effects of glucocorticoids and produces little or no suppression on the HPA function (Soyka, and Saxena, 1965;Fleisher and Pellecchia, 1965;Ackerman and Nolan, 1968 ;MacGregor et al, 1969;Easton et al, 1971). The present study based on the plasma cortisol responsiveness to ACTH also clearly indicates that the HPA function can be et al…”

Section: Discussionmentioning

confidence: 99%

Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man.

et al. 1980

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The relative potency in the hypothalamic-pituitary-adrenal (HPA) suppression of both prednisolone and betamethasone was examined in an acute study with normal volunteers and in a chronic study with glucocorticoid-treated patients. Circadian rhythm of plasma cortisol was studied after a single dose administration of 5 to 30 mg prednisolone or 0.5 to 3.0 mg betamethasone at 08 : 00 hr. Morning-rise of plasma cortisol occurred on the morning after the administration of 30 mg or less prednisolone but no morning rise was noted after the administration of 1.0 mg or more betamethasone. Plasma ACTH was slightly elevated on the morning after 30 mg prednisolone administration but showed low levels throughout the night after 3.0 mg betamethasone administration.Plasma cortisol responsiveness to ACTH was examined in patients before and during therapy with either prednisolone or betamethasone.The basal cortisol level was not suppressed and the responsivenessto ACTH remained nearly normal during long-term 5 mg prednisolone therapy, but these were completely suppressed during long-term 0.5 mg betamethasone therapy.The responsiveness to ACTH was nearly normal in patients receiving alternate-day therapy with prednisolone in such large doses as 50 or 60 mg every other day, but was completely suppressed in patients receiving 1.0 mg betamethasone every other day. The relative potency of betamethasone in acute and chronic suppressive effects on the HPA system seems to be much stronger than that of prednisolone inequivalent doses with comparable anti-inflammatory effects. It is also suggested that the alternate-day therapy with such long-acting steroids as betamethasone are useless in preventing HPA suppression.

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Section: Discussionmentioning

confidence: 99%

Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man.

et al. 1980

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“…Thus, minimal HPA disturbance would probably follow multiple small doses of steroid spaced so that there is no cumulative effect. Such treatment might be preferable to alternate day therapy which does not always give good symptom relief, although effects on the endocrine system are reduced (Ackerman & Nolan, 1968;Harter, Reddy & Thorn, 1963;Jasani, Boyle, Carson-Dick, Williamson, Taylor & Watson-Buchanan, 1968).…”

Section: Discussionmentioning

confidence: 99%

Recovery of hypothalamo‐pituitary‐adrenal function in the rat after prolonged treatment with betamethasone

Hodges

Mitchley

1970

British J Pharmacology

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Summary1. Betamethasone caused growth retardation, adrenal atrophy and impaired hypothalamo-pituitary-adrenal (HPA) activity in the rat. 2. In spite of the profound impairment, recovery of normal HPA function was rapid, but the growth retardation persisted.3. The ability of the pituitary gland to secrete basal corticotrophin (ACTH), recovered more rapidly and the adrenocorticotrophic response to stress less rapidly than the ability of the adrenal cortex to respond to ACTH. 4. The degree of HPA suppression was not determined by the total dose of steroid. 5. The possible significance of the results is discussed.

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“…Asthmatic patients did, however, show a suppression of plasma cortisol of 65.2% References [95% CI 10.5-67.8] and a significant suppression of plasma ACTH (adrenocorticotropic hormone) levels compared with effects of FP [21]. for budesonide in a previous study [22] suggested that systemic side-effects on the hypothalamus 23-55. pituitary adrenal axis are more dependent on persistent 8 Lönnebo A, Grahnén A, Jansson B, Brundin RM, Lingplasma levels than on high peak plasma concentrations [23]. of FP [24].…”

Section: Assaysmentioning

confidence: 99%

Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects

Thorsson¹,

Dahlström²,

Edsbäcker³

et al. 1997

Brit J Clinical Pharma

141

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Aims The present study was undertaken to see whether the difference in plasma cortisol suppression between single and repeated dosing of fluticasone propionate (FP) can be explained by systemic accumulation. Methods Twelve healthy subjects (six women) were given, in a crossover fashion, a single dose inhalation (1000 mg ) of FP via DiskhalerA and repeated inhalations (1000 mg twice daily) every 12 h during 7 days. There was a washout period of 2 weeks between the treatments. An intravenous dose of 20 mg FP was given as a reference. Plasma concentrations of FP for each treatment were determined by liquid chromatography plus tandem mass spectrometry. Plasma cortisol after the inhaled doses was determined using an immunoassay and was compared with baseline values. Results The average plasma concentration of FP was about 1.7 times higher after multiple inhalations than after a single dose. Systemic availability, mainly attributable to pulmonary deposition, was 15.6 [13.6-18.0]% of the nominal dose. Daytime plasma cortisol suppression vs baseline was 47 [20-65]% and 95 [93-97]% for the single and repeated doses, respectively. Conclusions To conclude, a slow elimination of FP leads to accumulation during repeated dosing. This accumulation may explain the marked decrease in plasma cortisol seen during treatment with fluticasone propionate within the clinical dose range.

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Studies on an Intermittent Corticosteroid Dosage Regimen

Cited by 339 publications

References 14 publications

Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man.

Relative potency in acute and chronic suppressive effects of prednisolone and betamethasone on the hypothalamic-pituitary-adrenal axis in man.

Recovery of hypothalamo‐pituitary‐adrenal function in the rat after prolonged treatment with betamethasone

Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects

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