Pharmacokinetic studies of prednisolone in children

Green, Orville C.; Winter, Robert J.; Kawahara, Frank S.; Phillips, Lawrence S.; Lewy, Peter; Hart, Robert L.; Pachman, Lauren M.; Lietman, Paul S.

doi:10.1016/s0022-3476(78)80529-0

Cited by 64 publications

(15 citation statements)

References 13 publications

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“…Wolthers et al [3]reported that administration of GH reversed the glucocorticoid induced protein catabolic effect detected in the present study, which is in accordance with other reports [1, 2, 4, 17]. A consistent finding in human studies is decreased IGF-I bioactivity in parallel with the protein catabolic effects of pharmacological doses of glucocorticoids [10, 12, 19, 20]. The exact nature of this decreased IGF-I bioactivity with unchanged/increased total IGF-I levels is unclarified.…”

Section: Discussionsupporting

confidence: 93%

“…Moreover, serum total IGF-I concentrations are normal or even elevated after both short-term and more prolonged exposure to glucocorticoids [1, 2, 5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]. Several studies have, however, shown reduced serum IGF bioactivity following glucocorticoid administration [10, 12, 19, 20]. This reduced bioactivity was not detectable when glucocorticoids were added to normal serum, which suggests the effect to depend on the generation of endogenous inhibitors [10].…”

Section: Introductionmentioning

confidence: 99%

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No Influence of Prednisolone on IGFBP-3 Proteolysis in Healthy Young Men

et al. 2001

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Aims: The impact of growth hormone (GH) and prednisolone on the GH/insulin-like growth factor (IGF) axis with special emphasis on IGF binding protein-3 (IGFBP-3) proteolysis was studied in 8 healthy adults in a double-blind cross-over study with four periods: (1) placebo; (2) s.c. GH 0.1 IU/kg/day; (3) oral prednisolone 50 mg/day, and (4) co-administration of GH and prednisolone. Methods: Each treatment period lasted for 4 days followed by a washout period of 10 days. We measured IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 by immunoassays, IGFBP-3 by Western ligand blotting (WLB) and finally in vitro IGFBP-3 proteolysis by a ¹²⁵I-IGFBP-3 degradation assay. Results: IGF-I levels increased by 99% during GH administration and 67% during co-administration of GH and prednisolone (p < 0.0005), whereas no significant change was seen during prednisolone alone. IGFBP-1 levels decreased 55% during the prednisolone period (p < 0.002), but the between period changes were not significant (p < 0.1). IGFBP-2 decreased 33% during co-administration of GH and prednisolone (p < 0.002). IGFBP-3 increased 12% during GH and 7% during co-administration of GH and prednisolone (p < 0.003 and p < 0.03 compared to placebo, respectively), whereas prednisolone alone induced no significant changes. IGFBP-3 measured by WLB did not change significantly, neither did IGFBP-3 proteolysis. Conclusions: Prednisolone administration induces only minimal changes in circulating components of the IGF axis and is not accompanied by alterations in IGFBP-3 proteolysis. This indicates that the metabolic effects of glucocorticoids do not depend on serum IGF-I.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

No Influence of Prednisolone on IGFBP-3 Proteolysis in Healthy Young Men

et al. 2001

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“…Thus, data obtained from oral dosing alone cannot distinguish between these two groups of patients. Similar magnitudes of variability were noted in peak prednisolone levels and prednisolone concentration-time profiles after oral prednisone or prednisolone was administered to patients with respiratory disease (11) and pediatric patients with various disease states (12). Bioavailability data in patients with kidney disease have been limited to studies in transplant patients.…”

Section: Discussionmentioning

confidence: 74%

Prednisolone Disposition in Cushingoid and Noncushingoid Kidney Transplant Patients*

Gambertoglio

Vincenti

Feduska

et al. 1980

The Journal of Clinical Endocrinology & Metabolism

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Little information is available on the disposition of prednisolone in kidney transplant patients and whether correlations exist between the pharmacokinetics and therapeutic or toxic effects of this drug. The present study was designed to determine the pharmacokinetics of prednisolone in six noncushingoid and six cushingoid transplant recipients. The elimination half-lives were not significantly different in the noncushingoid and cushingoid patients (2.3 vs. 3.3 h). However, other pharmacokinetic parameters were significantly lower in the cushingoid group: plasma clearance (147 vs. 82 ml/min) and volume of distribution (32 vs. 20 liters). In addition, the availability of prednisolone after oral prednisone administration was considerably variable (overall range, 27-108%) and was not significantly different between the two groups. Thus, in kidney transplant patients it appears that the plasma clearance and volume of distribution of prednisolone may distinguish between noncushingoid and cushingoid patients.

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“…Previous studies have demon¬ strated a decrease in serum IGF bioactivity in patients with Cushing's disease; the bioactivity returning to normal after treatment (Van den Brande & Du Cajú, 1974;Gourmelen et al 1982). A decrease in IGF bio¬ activity has also been reported following the intra¬ venous or oral administration of glucocorticoids to humans (Elders et al 1975;Green et al 1978) and rats (Mosier et al 1976). It has been suggested that this fall in IGF bioactivity occurs as a direct result of steroid inhibition of cartilage activity; indeed, direct addition of dexamethasone to the cartilage medium inhibited bioactivity as previously reported (Daughaday & Mariz, 1962).…”

Section: Discussionmentioning

confidence: 94%

The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers

Miell

Taylor²,

Jones³

et al. 1993

Journal of Endocrinology

107

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Glucocorticoids inhibit somatic growth in man and laboratory animals, and have long been regarded as suppressors of both stimulated GH secretion and insulin-like growth factor (IGF) activity. Recent evidence suggests, however, that glucocorticoids can be potent GH secretagogues in their own right with concomitant increases in circulating IGF-I levels. IGFs circulate tightly bound to a group of high-affinity binding proteins (IGFBPs) which modulate their actions. In order to investigate the effects of glucocorticoids on serum levels of IGFs and IGFBPs, normal male volunteers were sampled over 24-h periods before and directly after treatment with dexamethasone (2 mg twice daily) for 96 h. Following dexamethasone administration, all volunteers showed a marked increase in mean +/- S.E.M. IGF-I levels over the 24-h sampling period (292.2 +/- 31.8 before dexamethasone, 425.9 +/- 37 micrograms/l after dexamethasone, P < 0.005); there was no change in mean IGF-II levels. Integrated mean insulin levels were raised by dexamethasone treatment (50 +/- 4.6 before dexamethasone, 117 +/- 13.4 mU/l after dexamethasone, P = 0.002) and IGFBP-1 was significantly suppressed (42.9 +/- 8.2 before dexamethasone, 28.0 +/- 7.9 micrograms/l after dexamethasone, P < 0.001). IGFBP-2 levels were similarly suppressed after dexamethasone (319.5 +/- 24.5 before dexamethasone, 214.8 +/- 8.5 micrograms/l after dexamethasone, P = 0.002), and there was a significant increase in IGFBP-3 levels from 3.24 +/- 0.25 to 3.67 +/- 0.32 mg/l (P = 0.0153). Mean IGF bioactivity over the sampling period after dexamethasone was reduced by approximately 60% (0.93 +/- 0.39 before dexamethasone, 0.39 +/- 0.05 U/ml after dexamethasone, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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Pharmacokinetic studies of prednisolone in children

Cited by 64 publications

References 13 publications

No Influence of Prednisolone on IGFBP-3 Proteolysis in Healthy Young Men

No Influence of Prednisolone on IGFBP-3 Proteolysis in Healthy Young Men

Prednisolone Disposition in Cushingoid and Noncushingoid Kidney Transplant Patients*

The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers

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