Diurnal variation of prednisolone binding to serum corticosteroid‐binding globulin in man

Angeli, Alberto; Frajria, Roberto; Paoli, R. De; D, Fonzo; Ceresa, F

doi:10.1002/cpt197823147

Cited by 54 publications

(19 citation statements)

References 10 publications

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“…(1981). However, since transcortin also binds other steroids such as cortisol, which is subject to diumal variation, it is possible that prednisolone was studied in the presence of competing amounts of cortisol (Angeli et al, 1978).…”

Section: Resultsmentioning

confidence: 99%

The binding of prednisolone in human serum and to recrystallized human albumin in vitro.

Steele¹,

Hawksworth²,

Barber³

1982

Brit J Clinical Pharma

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1 Prednisolone binding in human serum and to recrystallized human serum albumin was measured by continuous ultrafiltration. 2 At serum concentrations of prednisolone up to 0.6 micron, 95.0% was bound but at higher concentrations the binding became non‐linear falling to 80.5% at 1.8 microns. At even higher concentrations binding in serum became linear again and paralleled the binding to albumin which was linear throughout the entire range of prednisolone concentrations. 3 A binding model was proposed which included a saturable component attributable to binding to transcortin and a non‐saturable binding to albumin. 4 Computer simulations using the experimentally determined binding parameters of the model indicated that binding in serum was critically dependent on transcortin concentration and almost independent of albumin concentration.

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Section: Resultsmentioning

confidence: 99%

The binding of prednisolone in human serum and to recrystallized human albumin in vitro.

Steele¹,

Hawksworth²,

Barber³

1982

Brit J Clinical Pharma

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“…Animal studies have demonstrated a circadian variation in CBG concentrations with a gradual increase throughout the day with peak concentrations attained at 1800 h, and a subsequent decline during the night hours reaching nadir concentrations at 0600 h (Hsu & Khun 1988, Meaney et al 1992. Although similar studies are lacking in humans, a circadian variation of CBG binding capacity for prednisolone, with maximum binding observed at midnight and minimum binding observed at 0800 h, has been reported in healthy subjects (Angeli et al 1978). Alternatively, the decrease in cortisol clearance in the evening may relate to the circadian variation in ACTH secretion.…”

Section: Discussionmentioning

confidence: 98%

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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“…The reported circadian variation in prednisolone serum binding (Angeli et al, 1978) has led to speculation regarding circadian variation in prednisolone disposition (Pickup, 1979;McAllister et al, 1981a). Because during continuous therapy, the free concentration of a drug in plasma is determined only by dose rate and free clearance, changes in plasma protein binding will not alter the concentration of physiologically active unbound prednisolone.…”

Section: Time Ofadministrationmentioning

confidence: 99%

“…Circadian variations in the capacity of plasma to bind prednisolone have been reported, in which maximum binding occurred at midnight with a minimum at 08.00 h, and which showed an inverse relationship to plasma cortisol concentrations (Angeli et al, 1978). This report led to the suggestion that circadian variations in cortisol concentrations might produce alterations in prednisolone disposition (Pickup, 1979), but no changes in area under the total prednisolone plasma concentration-time curve were found after oral doses of approximately 0.3 mg/kg given at 08.00 h and 20.00 h (McAllister et al, 1981a).…”

Section: Introductionmentioning

confidence: 99%

Alterations in prednisolone disposition as a result of time of administration, gender and dose.

Meffin¹,

Brooks²,

Sallustio³

1984

Brit J Clinical Pharma

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1 The disposition of total and free prednisolone has been studied in four male and four female volunteers, each of whom received an intravenous dose of 0.075 mg/kg (low) and 1.5 mg/kg (high) of prednisolone at both 06.00 h and 18.00 h. 2 For the low dose, free prednisolone clearance was 14% lower (P = 0.012) and time-averaged prednisolone free fraction was 22% higher (P < 0.001) in the morning, there being no circadian difference in total prednisolone clearance. There was no circadian differences in prednisolone disposition at the high dose. These findings are consistent with a mechanism in which cortisol causes a simultaneous competitive inhibition of prednisolone clearance and plasma protein binding at low, but not at high prednisolone doses. 3 Prednisolone clearance was higher in female than in male subjects, the mean increase being 18% (P = 0.022) for total prednisolone and 21% (P = 0.036) for free prednisolone. 4 Mean total prednisolone clearance and steady-state distribution volume were two-fold higher at the high vs the low dose (P < 0.001), but free prednisolone clearance showed a dose dependent decrease of 11% (P = 0.019). There was no change in free prednisolone steady-state distribution volume.

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Diurnal variation of prednisolone binding to serum corticosteroid‐binding globulin in man

Cited by 54 publications

References 10 publications

The binding of prednisolone in human serum and to recrystallized human albumin in vitro.

The binding of prednisolone in human serum and to recrystallized human albumin in vitro.

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

Alterations in prednisolone disposition as a result of time of administration, gender and dose.

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