Pharmacokinetics of prednisolone after high doses of prednisolone hemisuccinate

Derendorf, Hartmut; Rohdewald, Peter; Rehder, J.; Barth, Jürgen; Neveling, D.

doi:10.1002/bdd.2510060408

Cited by 23 publications

(9 citation statements)

References 10 publications

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“…1,6,30 The concentration upswing of PLN was rapid, followed by a slower washout phase. 12,30,[32][33][34] Similar or larger values of IIV were reported in more distinct populations that included adults and/or children with immunemediated diseases. 24,31 Equilibrium of PLN between different media was reached rapidly as there was no observable delay, consistent with fast binding of PLN to transport proteins.…”

Section: Discussionsupporting

confidence: 71%

“…Most studies reported variable ratios of salivary and total plasma PLN over time. [12][13][14][15] All the former issues are dealt with in our study because we used a robust and sensitive method for direct measurement of PLN and PN in saliva and both free and total concentrations of these steroids in serum. [13][14][15] One study reported good agreement between (calculated) free plasma and salivary levels of PLN, yet did not advise the use of saliva for drug monitoring because the then available assays lacked sensitivity in the low salivary concentration ranges.…”

Section: Discussionmentioning

confidence: 99%

“…1,8 PLN shares great similarity with endogenous cortisol, which shows a comparable protein-binding profile. [12][13][14][15] Recently, we have reported a method for simultaneous measurement of PLN and PN in saliva, serum, and ultrafiltrate that demonstrated promising results with respect to the relationship between free serum PLN concentrations and salivary PLN concentrations. 1,2,8 Measurement of unbound PLN in blood is time consuming as it requires separation of the unbound and bound fractions.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring Prednisolone and Prednisone in Saliva

Teeninga

Zheng

Freijer

et al. 2013

Therapeutic Drug Monitoring

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Monitoring Prednisolone and Prednisone in Saliva

Teeninga

Zheng

Freijer

et al. 2013

Therapeutic Drug Monitoring

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“…Most intravenous pharmacokinetic studies previously performed used hydrocortisone hemisuccinate as a water soluble pro-drug (Toothaker & Welling 1982). However, after intravenous hemisuccinate administration of other corticosteroids, substantial amounts of the prodrug could be found in the urine making it a less than optimum standard for the assessment of bioavailability (Derendorf et al 1985, Möllmann et al 1988.…”

Section: Introductionmentioning

confidence: 99%

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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“…Therefore, the total concentration of prednisolone decreases more slowly in plasma than the total concentration in saliva which mainly reflects the free fraction (34). If the free drug fraction varies with the plasma concentration, the saliva/plasma ratio cannot be constant during all pharmacokinetic phases.…”

Section: Protein Bindingmentioning

confidence: 99%

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The determination of salivary drug concentrations is one of the major domains for the application of saliva in laboratory medicine. Its usefulness, however, has been criticized for many drugs because of the variability of the saliva/plasma concentration ratio (saliva/plasma ratio).Considering saliva as a model for transmembrane transport, drugs can be divided into 4 groups. The first group is characterized by a saliva/plasma ratio less than 1.0. In extreme cases a drug with negligible transport is either not detectable in saliva or is found in very low concentrations which are hard to measure or difficult to interpret.A second group leads to saliva/plasma ratios which are approximately constant and about 1.0 under most of the conditions studied. This group is ideal for monitoring salivary drug concentrations.A third group is sufficiently transferred into saliva, but the saliva/plasma ratio varies under different conditions. The reason for this variation is that the transport is influenced by several factors including an active transport mechanism. The varying influence of these factors on the saliva/plasma ratio largely depends on the physicochemical characteristics of the particular substance.In a fourth group very high saliva/plasma ratios are observed primarily due to the degree of ionization of weak bases.A representative of each group is presented with its saliva/plasma ratio and its physico-chemical properties: ceftazidim, ethanol, digoxin and prilocain. In all cases the salivary concentration probably reflects the intracellular concentration in target tissues. All examples confirm saliva as an ideal in vivo model for the study of transmembrane transport in the human organism.

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Pharmacokinetics of prednisolone after high doses of prednisolone hemisuccinate

Cited by 23 publications

References 10 publications

Monitoring Prednisolone and Prednisone in Saliva

Monitoring Prednisolone and Prednisone in Saliva

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

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