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Results for “Prednisolone”

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PubMed1983

Urinary 6 beta-hydroxyprednisolone excretion indicates enhanced prednisolone catabolism.

Patients with enhanced catabolism of prednisolone exhibit a reduction in steroid efficacy. Since prednisolone never reaches steady state at the usual dosage, the clearance rate can only be estimated by determining the area under the plasma concentration-time curve after an i.v. dose of prednisolone. To obviate that time-consuming procedure for screening of patients with enhanced prednisolone metabolism, we developed a quantitative assay for 6 beta-hydroxyprednisolone in urine to determine whether the urinary excretion of 6 beta-hydroxyprednisolone increases concomitantly with the clearance rate of total and of unbound prednisolone in subjects with an enhanced catabolism of prednisolone. The results are given separately for males and females because there is some debate as to whether females compared to males exhibit a higher capacity of the liver to hydroxylate steroids at the sixth position. Before and during the administration of phenytoin the total body clearance of total and of unbound prednisolone and the urinary excretion of prednisolone and of 6 beta-hydroxyprednisolone were determined in six female and eight male volunteers. The fraction of the i.v. dose of prednisolone excreted in urine as 6 beta-hydroxyprednisolone was higher in females than in males (p less than 0.001) and increased during phenytoin dosing from 6.4%-10.4% (range) to 15.6%-20.4% in females and from 2.4%-7.2% to 12.2%-18.3% in males. The ratio of 6 beta-hydroxyprednisolone to prednisolone in urine increased linearly with the nonrenal clearance of both total and unbound prednisolone. This is the first demonstration that the fractional excretion of 6 beta-hydroxyprednisolone increased after the induction of the microsomal liver enzymes. Thus measurements of urinary 6 beta-hydroxyprednisolone excretion may be of potential value to detect patients with enhanced catabolism of prednisolone.

Adult↗

PubMed1992

Evaluation of dose-related pharmacokinetics and pharmacodynamics of prednisolone in man.

The pharmacokinetics and pharmacodynamics of prednisolone were evaluated in normal male volunteers. Seven subjects completed 3 phases: 16.4- and 49.2-mg iv prednisolone, and a phase with no drug to assess baseline responses. Plasma concentrations of prednisolone and urine concentrations of prednisolone and 5 metabolites were assayed by HPLC. Protein binding of prednisolone was measured by ultrafiltration. The polyexponential disposition of free and total plasma prednisolone were evaluated and apparent parameters were compared between doses. Suppression of plasma cortisol and alterations in blood basophil and helper-T cell trafficking were used as pharmacodynamic indices. Pharmacodynamic models were used to relate total or free plasma prednisolone concentrations to each of these effects generating response parameters and IC50 (50% inhibitory) concentrations common to both doses. The pharmacokinetics of total drug were comparable to previous findings with CL and Vss increasing with dose. Free prednisolone exhibited slight capacity-limited elimination and distribution as CL and Vss decreased with the larger dose. Pharmacodynamic models jointly fitting all three phases characterized the suppression/trafficking phenomena equally well with use of total or free drug concentrations. In each case the models provided realistic values of parameters relating to steroid sensitivity--in particular IC50--and to the underlying physiology of the affected systems. This study comprehensively elucidates the complexities of prednisolone pharmacokinetics and demonstrates how plasma concentration--time profiles of total or free prednisolone can be utilized for evaluation of prednisolone pharmacodynamics.

Adult↗

PubMed2000

Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis.

Glucocorticoid-induced osteoporosis has been reported to be caused by enhanced bone resorption and suppressed bone formation. To clarify whether administration of vitamin K, which enhances bone formation, prevents prednisolone-induced loss of bone mineral density (BMD), a randomized, prospective, controlled study was conducted on 20 patients with chronic glomerulonephritis scheduled for treatment with prednisolone. All patients were initially treated with 0.8 mg/kg body weight/day of prednisolone (maximum of 40 mg) for 4 weeks, tapering to 20 mg/day over approximately 6 weeks. Ten patients received prednisolone alone (Group 1), and the other 10 patients received prednisolone plus 15 mg of menatetrenone, vitamin K, three times per day (Group 2). BMD of the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) and biochemical markers of bone metabolism in blood and urine were evaluated before and 10 weeks after administration of prednisolone alone or with menatetrenone. In Group 1, treatment with prednisolone significantly reduced BMD of the lumbar spine from 1.14 +/- 0.12 to 1.10 +/- 0.11 g/cm2 (P = 0.0029). Serum intact osteocalcin and procollagen type I C-peptide (PICP) concentrations, biochemical markers of bone formation, were markedly reduced. A biochemical marker of bone resorption, urinary excretion of deoxypyridinoline, was significantly reduced. In Group 2, prednisolone-induced reduction of BMD was prevented by menatetrenone administration (1.09 +/- 0.09 to 1.07 +/- 0.07 g/cm2, P = 0.153). Menatetrenone prevented reduction of PICP concentration by prednisolone but not in serum intact osteocalcin concentration and urinary excretion of deoxypyridinoline. Thus, treatment with prednisolone resulted in loss of BMD of the lumbar spine associated with suppression of both bone formation and bone resorption. Menatetrenone is a useful agent in preventing prednisolone-induced loss of BMD.

Absorptiometry, Photon↗

PubMed1992

Altered prednisolone pharmacokinetics in patients with cystic fibrosis.

Prednisolone pharmacokinetics were evaluated in eight patients with cystic fibrosis (CF) (aged 1.8 to 20 years) by assessing absorption of orally administered prednisone (in its active form, prednisolone) and elimination of prednisolone after intravenous administration. After an overnight fast, subjects received intravenously administered doses of prednisolone or orally administered doses of prednisone, 40 mg/1.73 m2 body surface area, before a standardized breakfast. Serial blood samples were collected for 12 hours and analyzed for prednisolone concentration. Prednisolone pharmacokinetics were compared in eight age-matched patients with asthma who required steroids after intravenous administration of prednisolone. The prednisolone pharmacokinetic parameters derived demonstrated an increased total clearance (by 60%), an increased volume of distribution (by 46%), a lower peak concentration (by 35%), and no difference in elimination half-life in patients with CF compared with those with asthma. Bioavailability averaged 88.4% +/- 20.1% of the administered dose. Prednisolone clearance was markedly increased in those with CF. There was a proportional increase in nonrenal clearance, with no difference in renal clearance in those with asthma or CF. The plasma protein binding of prednisolone was only slightly decreased in patients with CF and did not account for the observed pharmacokinetic alteration. The marked increase in prednisolone clearance may necessitate the use of more frequent or higher doses of this steroid in the treatment of patients with CF, leading to a potentially less favorable benefit/risk ratio.

Administration, Oral↗

PubMed1988

Altered metabolism and decreased efficacy of prednisolone and prednisone in patients with hyperthyroidism.

To evaluate the effect of hyperthyroidism on the protein binding and metabolism of prednisolone, eight subjects with hyperthyroidism were investigated before and after thyroid status returned to normal. Hyperthyroidism was associated with a reduced volume of distribution of prednisolone, a decreased systemic availability of prednisolone after oral prednisone, a displacement of the prednisolone in equilibrium with prednisone equilibrium toward prednisone, and an increased nonrenal clearance of unbound prednisolone in the presence of an impaired 6 beta-hydroxyprednisolone formation. After oral prednisone or intravenous prednisolone, patients with hyperthyroidism had lower albumin-bound, transcortin-bound, and unbound concentrations of prednisolone but normal affinities of albumin and transcortin for prednisolone binding. These differences in prednisolone plasma concentrations were biologically relevant, because the capacity of these plasma samples to inhibit allogeneically stimulated lymphocytes was lower by 70% in the hyperthyroid than in the euthyroid state. Thus hyperthyroidism reduces the biologic effect of prednisolone and exhibits a differential effect on various enzymes involved in the catabolism of prednisolone.

Administration, Oral↗

PubMed1982

Prednisone and prednisolone bioavailability in renal transplant patients.

Prednisone and prednisolone are drugs with the potential for therapeutic inequivalence due to bioavailability problems. The objective of our study was to compare the systemic bioavailability of prednisolone from oral prednisone and prednisolone. Nine kidney transplant patients receiving prednisone (12.5 to 22.5 mg per day) were administered, in a randomized fashion, the same dose of oral prednisone (Deltasone), oral prednisolone (Delta-cortef) and intravenous prednisolone (Hydeltrasol). Prednisolone and prednisone levels were measured using a specific high-pressure liquid chromatographic assay. Since prednisolone exhibits dose-dependent pharmacokinetics because of nonlinear plasma protein binding, bioavailability from oral prednisone and oral prednisolone, compared to the intravenous dose, was 84.5 +/- 17.8% and 95.5 +/- 17.6% using unbound drug concentrations. These differences were not statistically significant. Furthermore, no significant differences were observed between the two oral formulations in peak prednisolone levels, time of peak levels or half-life using either total or unbound drug concentrations. The results from our study indicate that both of the oral preparations tested provide similar bioavailability of active prednisolone and the conversion of prednisone to prednisolone occurs rapidly.

Administration, Oral↗

PubMed1982

Intensive immunosuppression versus prednisolone in the treatment of connective tissue diseases.

Intensive immunosuppression (IIS) was compared with prednisolone alone over a 2-year period in the treatment of severe connective tissue diseases. IIS consisted of 15 daily infusions of 750 mg antilymphocyte globulin (ALG), azathioprine 2.5 mg/kg/day, and prednisolone reducing from 150 mg, followed by maintenance azathioprine and prednisolone. The initial dose for prednisolone by itself was 60 mg and patients not responding to this regimen over a minimum of one month were then given IIS. Forty-one patients with life-threatening or severely disabling polyarteritis nodosa (PAN), dermatomyositis/polymyositis (DM), or systemic lupus erythematosus received one or other treatment. All 11 patients who received IIS for PAN remitted. Ten of these had renal impairment which was reversed or halted with IIS, and in 6 of these renal function had been deteriorating with prednisolone alone. One patient died of pneumonia in renal failure 9 months later but with PAN in remission. Two further patients, neither having renal involvement, achieved remission with prednisolone alone. Early cytotoxic treatment would seem to be indicated in PAN when there is renal involvement. Two patients with DM entered remission or prednisolone alone. The remaining 12, of whom 5 had failed steroid therapy, received IIS. Improvement or halting of deterioration was achieved in all 12 with best results in those without marked muscle wasting consequent to disease of long duration. The results suggest that IIS may be a useful adjunct in those patients failing to respond to prednisolone. IIS seemed no more effective than prednisolone alone in the treatment of the 14 patients with SLE and in particular lupus nephritis. Flares in disease activity were common in both groups and appeared to be related to prednisolone dosage. IIS was generally well tolerated, though infection occurred in 2 patients. Vertebral collapse or osteonecrosis of the femoral head occurred in 3 patients following IIS, all of whom had been previously receiving prednisolone for long periods.

Adolescent↗

PubMed1999

A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects.

OBJECTIVES: To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS: One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS: The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm. CONCLUSIONS: This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses.

Adult↗

PubMed1986

Effects of dietary sodium chloride loading on parathyroid function, 1,25-dihydroxyvitamin D, calcium balance, and bone metabolism in female rats during chronic prednisolone administration.

The effects of dietary sodium chloride supplements (8 g/100 g diet) on parathyroid function, serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], calcium balance, bone metabolism, and bone composition were studied in rats treated with prednisolone (2 mg/kg w X day) for 12 weeks. Animals on a low calcium diet (0.1% Ca) received the following treatments: group 1, control; group 2, NaCl; group 3, prednisolone; group 4, NaCl plus prednisolone. Parathyroid function was assessed indirectly from urinary cAMP excretion: bone resorption was estimated by studying urinary hydroxyproline excretion and mobilization of 45Ca from bone. Dietary salt loading increased the urinary excretion of calcium, 45Ca, cAMP, and hydroxyproline and raised serum 1,25-(OH)2D and net calcium absorption, but lowered calcium retention, femoral calcium, and total body calcium. Prednisolone slowed body growth and lowered net calcium absorption, calcium retention, femoral calcium, and total body calcium. Urinary calcium excretion was higher in rats receiving salt and prednisolone in combination than in animals taking salt without prednisolone, but other responses to salt and prednisolone were independent. Thus, salt and prednisolone each elicit osteopenia, and salt causes bone loss in rats receiving prednisolone. The osteopenic effect of salt is attributed to primary augmentation of urinary calcium excretion and secondary increases in PTH-medicated bone resorption. Although salt-treated rats have higher blood levels of 1,25-(OH)2D, bone loss occurs because alimentary calcium absorption is not elevated sufficiently to offset urinary calcium losses. Prednisolone lowers bone formation and net calcium absorption without lowering serum 1,25-(OH)2D values. The parathyroid-vitamin D axis remains intact in prednisolone-treated rats, as they show increases in PTH and 1,25-(OH)2D after salt treatment.

Animals↗

PubMed1991

The pharmacokinetics of plasma total and free prednisolone during an alternate-day regimen.

To determine the pharmacokinetic changes of prednisolone associated with an alternate-day regimen, 12 patients with various diseases were studied longitudinally. There were 9 patients (6 with systemic lupus erythematosus, 2 with sarcoidosis and one with polymyositis), who were treated with prednisolone (daily period) and subsequently put on an alternate-day regimen (alternate-day period). In 2 of the other patients (one with systemic lupus erythematosus and one with multiple sclerosis), the alternate-day regimen was preceded by the daily regimen, and subsequently an intermittent regimen consisting of 4 consecutive days on therapy and 3 days off therapy was followed. In the remaining patient with systemic lupus erythematosus, the treatment with the alternate-day regimen was initiated and followed throughout the treatment period. The mean duration and the mean total administered dose during the study were 1.1 months and 1.9 g in the daily period, and 7.8 months and 7.7 g in the alternate-day period. The test was done and blood was drawn for 6 hours after an intravenous administration of 20 mg prednisolone (0.36 mg/kg on the average) at the end of the respective regimen periods. In the daily period and the on-day of the alternate-day regimen, the pharmacokinetic study of iv prednisolone injection was done before the ingestion of oral prednisolone. The off-day test was done the next morning of the on-day. Plasma total and free prednisolone concentrations were measured by RIA. On-day and off-day tests in the alternate-day period were performed during the same week. The mean half life of both total and free prednisolone was prolonged significantly in the daily period and during the on-day and off-day of the alternate-day regimen compared with the pretreatment values. The mean metabolic clearance rates (MCR) of both total and free prednisolone decreased significantly in the daily period and during the on-day and off-day of the alternate-day period in comparison with the pretreatment values. No significant difference was found between either mean half life or MCR during the on-day and off-day of the alternate-day period. These findings were in contrast with our previously observed prednisolone pharmacokinetics during the intermittent regimen (4 days on therapy and 3 days off therapy within one week), in which pharmacokinetic parameters during the on-day (after 3 days of prednisolone ingestion) and off-day (after 3 off-days of prednisolone ingestion) periodically changed and were similar to those in the pre-treatment period and during the daily therapy period, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

Pharmacokinetics/pharmacodynamics of ketoconazole-prednisolone interaction.

Ketoconazole is commonly used in patients with fungal infections during immunosuppressive therapy with prednisolone. Ketoconazole inhibits mixed function oxidases, enzymes responsible for the catabolism of prednisolone, and might, by that mechanism, increase prednisolone concentrations and thus, the immunosuppressive effect of prednisolone. On the other hand, ketoconazole has been found to bind to the glucocorticoid receptor and, thereby, to function as a glucocorticoid antagonist in cultured cell preparations. In order to establish whether ketoconazole enhances or attenuates the immunosuppressive effect of prednisolone, the influence of ketoconazole on the kinetics of prednisolone and on the delayed hypersensitivity response was assessed in mice. Ketoconazole increased prednisolone concentrations, measured by high pressure liquid chromatography, in mice given a single dose of prednisolone or a continuous prednisolone treatment for 17 days. At four different doses of prednisolone administered for 17 days, the glucocorticoid therapy-associated inhibition of the delayed hypersensitivity response to keyhole limpet hemocyanin was enhanced by ketoconazole. Thus, coadministration of ketoconazole with prednisolone increases the exposure to the steroid and enhances the immunosuppressive effect.

Animals↗

PubMed2000

The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone.

OBJECTIVE: To examine the possible effect of itraconazole on the pharmacokinetics and pharmacodynamics of orally administered prednisolone. METHODS: In this double-blind, randomised, two-phase cross-over study, ten healthy subjects received either 200 mg itraconazole or placebo orally once a day for 4 days. On day 4, 20 mg prednisolone was given orally. Plasma concentrations of prednisolone, cortisol, itraconazole, and hydroxyitraconazole were determined by means of high-performance liquid chromatography up to 47 h. RESULTS: Itraconazole increased the total area under the plasma prednisolone concentration-time curve by 24% (P < 0.001) and the elimination half-life of prednisolone by 29% (P < 0.001) compared with placebo. The peak plasma concentration and time to the peak of prednisolone were not affected by itraconazole. The mean morning plasma cortisol concentration, measured 23 h after the ingestion of prednisolone, during the itraconazole phase was 73% of that during the placebo phase (P < 0.001). CONCLUSIONS: The observed minor interaction between itraconazole and oral prednisolone is probably of limited clinical significance. The susceptibility of prednisolone to interact with CYP3A4 inhibitors is considerably smaller than that of methylprednisolone, and itraconazole and probably also other inhibitors of CYP3A4 can be used concomitantly with prednisolone without marked changes in the effects of this corticosteroid.

Adult↗

PubMed1990

Pharmacodynamic modeling of lymphocytopenia and whole blood lymphocyte cultures in prednisolone-treated individuals.

In this study, we describe the time course of the influence of a single oral dose of prednisolone (10 mg) in man on the proliferative response of peripheral blood lymphocytes in whole blood. The data were fitted to an integrated pharmacokinetic-pharmacodynamic model, relating the plasma concentrations of prednisolone to its effect. The determination of prednisolone-induced lymphocytopenia and monocytopenia in vivo and the assessment of the influence of varying lymphocyte and monocyte numbers on proliferative responses in vitro enabled us to calculate the relative contributions of several prednisolone-induced effects to the diminished lymphoproliferative responses in whole blood after administration of prednisolone in vivo. We demonstrate that the decrease of the proliferative response in whole blood lymphocyte cultures stimulated with a monoclonal antibody directed against CD3 is mainly determined by the time course of the prednisolone-induced lymphocytopenia. The time course of the monocytopenia and the relative changes in the CD4+ and CD8+ T-cell subpopulations induced by prednisolone and the direct inhibitory effect of the changing plasma concentrations of the drug also contribute to the decrease of aCD3-stimulated whole blood lymphocyte cultures to some extent. The decrease of the proliferative response in whole blood lymphocyte cultures stimulated with a horse anti-human lymphocyte serum closely followed the time course of the lymphocytopenia induced by prednisolone. However, this response remained decreased for a longer period of time than could be expected on the basis of the prednisolone-induced lymphocytopenia in vivo. A possible mechanism which might explain this discrepancy between the prednisolone-induced effects in vivo and in vitro will be discussed.

Administration, Oral↗

PubMed2005

The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome.

During pregnancy the placental 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) enzyme inactivates prednisolone by interconversion into prednisone, protecting the fetus from high levels of prednisolone. Recent reports suggest decreased placental 11beta-HSD2 activity in pregnancies complicated by preeclampsia. The purpose of our investigation was to study the transplacental passage of prednisolone in patients suffering from early preterm HELLP syndrome, a severe complication of preeclampsia. We examined the maternal and umbilical cord plasma concentration of prednisolone in nine women receiving 50 mg of prednisolone twice a day. Samples were obtained during caesarean section at a gestational age between 27 and 31 weeks. Mean fetal concentration was 10-fold lower as compared to maternal prednisolone concentration (mean+/-SD 52.8 nmol/L+/-27.0 vs. 477.5 nmol/L+/-300, p<0.01). A significant correlation was found between the last dose of prednisolone to delivery interval and the fetal prednisone concentration (Spearman's correlation coefficient r=-0.946, p<0.000). Our data demonstrate unimpaired placental 11beta-HSD2 activity in patients suffering from HELLP syndrome at early gestational age as shown by both a 10-fold lower fetal prednisolone concentration as compared to the mother and a strong correlation between the last dose of prednisolone to delivery interval and the fetal prednisone concentration. Prednisolone may therefore have less effect on the fetus than betamethasone or dexamethasone.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2000

Effects of budesonide and prednisolone on hepatic kinetics for urea synthesis.

BACKGROUND/AIMS: Glucocorticoids upregulate hepatic urea synthesis and cause protein breakdown to prevail over synthesis, releasing amino acids into the blood stream and increasing the substrate supply for hepatic urea synthesis. Budesonide is a new generation glucocorticoid that may be used for treatment of inflammatory diseases, e.g. Crohn's disease and autoimmune hepatitis. Due to its extensive first-pass metabolism in the liver, it has a potential adverse effect profile superior to that of prednisolone. Little attention has been directed towards differences in nitrogen catabolic properties between budesonide and prednisolone. METHODS: Eight normal male subjects (age 20-44 years; BMI 21.6-28.2 kg/m2) were randomly studied 3 times: 1) At baseline, 2) after 6 days of prednisolone (50 mg/day), and 3) after 6 days of budesonide (9 mg/ day). We measured urea nitrogen synthesis rates (UNSR) and blood alpha-amino-nitrogen (N) levels before, during, and after a 3-h constant infusion of alanine (2 mmol/(kg BW x h)). UNSR was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in body water. The slope of the linear relationship between UNSR and amino-N concentration represents the hepatic kinetics of conversion of amino- to urea-N, and is denoted the functional hepatic nitrogen clearance (FHNC). RESULTS: Prenisolone, but not budesonide, administration increased basal blood and amino nitrogen concentrations (3.5 +/- 0.1 mmol/l (control) vs 3.8 +/- 0.1 mmol/l (prednisolone) (p<0.05) and 3.6 +/- 0.1 mmol/l (budesonide) (NS). Basal UNSR values were significantly increased following prednisolone (23.3 +/- 6.5 (control) vs 51.2 +/- 6.3 (prednisolone) (p<0.05)), while budesonide had no effect on basal UNSR (33.7 +/- 4.2 (budesonide) (NS)). Prednisolone administration increased FHNC (from 24.6 +/- 4.7 l/h (control) to 47.3 +/- 5.9 l/h (prednisolone) (p<0.05). Budesonide administration did not significantly increase FHNC (33.7 +/- 4.2 l/h (budesonide), (vs control; p=0.12, vs prednisolone: p<0.05)). CONCLUSIONS: Prednisolone administration led to increased levels of amino acids in blood and loss of N as urea, the latter in part due to a specific hepatic mechanism as shown by the increased FHNC. Budesonide led to unaltered levels of amino acids in blood, no changes in loss of N as urea, and unaltered hepatic kinetics for urea synthesis. Thus, oral budesonide administration had very limited effects on the hepatic contribution to nitrogen homeostasis and metabolism via urea synthesis, making treatment with budesonide superior to that of conventional glucocorticoids in this respect.

Adult↗

PubMed1987

Prednisolone and posttransplantation hypertension in rat renal allograft recipients.

Rat recipients of renal allografts and unilaterally nephrectomized control rats were studied to evaluate the response in blood pressure to prednisolone in diverse doses, and to determine the dosage required to achieve adequate immunosuppression without undue complication of hypertension. While a continuous infusion of 2 mg/kg/day or more of prednisolone proved effective in prolonging allograft survival time, this dosage increased the blood pressure of recipients as well as unilaterally nephrectomized control rats. In contrast to control rats, the recipients remained hypertensive after the cessation of prednisolone administration. This suggests that the high blood pressure observed during prednisolone administration was due to its hypertensive action. On the other hand, the high blood pressure remaining after cessation of the prednisolone administration is likely to be caused by an incomplete prevention of rejection. If recipients had received a transfusion of donor-strain blood prior to transplantation in combination with the infusion of 2 mg/kg/day or more of prednisolone, they became normotensive when the prednisolone infusion was ceased. By reducing the prednisolone dosage to 1 mg/kg/day in combination with donor-strain blood pretreatment, hypertension could also be eliminated during the first two weeks. In conclusion, effective immuno suppression can be achieved with prednisolone in rats, without inducing hypertension, provided prednisolone is administered at a low dosage in combination with adjuvant immunosuppression--i.e., donor-strain blood pretreatment.

Animals↗

PubMed2001

No influence of prednisolone on IGFBP-3 proteolysis in healthy young men.

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 (125)I-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.

Adult↗

PubMed1998

A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group.

We compared prednisolone (PRED) and azathioprine (AZA) versus prednisolone alone in the treatment of MG. Prednisolone alone or combined with azathioprine is widely used in the treatment of MG, but no randomized placebo-controlled comparative trial data are available. The prednisolone dose and clinical outcome were compared in a multicenter randomized double-blind study of 34 MG patients who were followed up for 3 years. One group (PRED + AZA) received prednisolone (on alternate days) plus azathioprine (2.5 mg/kg); the other group received prednisolone on alternate days plus placebo (PRED + PLAC). Initial high-dose prednisolone (1.5 mg/kg on alternate days) was tapered at remission to the minimal dose required to maintain remission. The prednisolone dose did not differ significantly between the two groups at 1 year (median values: PRED + AZA, 37.5 mg on alternate days; PRED + PLAC, 45 mg on alternate days) but was reduced at 2 and 3 years in the PRED + AZA group (median value at 3 years: PRED + AZA, 0 mg on alternate days; PRED + PLAC, 40 mg on alternate days; p=0.02). Relapses and failures to remit over the 3 years were more frequent in the PRED + PLAC group. There was a sharp rise in the anti-acetylcholine receptor (AChR) titers in the PRED + PLAC group at 2 years. Incidence of side effects was slightly less in the PRED + AZA group. Azathioprine as an adjunct to alternate day prednisolone in the treatment of antibody-positive generalized MG reduces the maintenance dose of prednisolone and is associated with fewer treatment failures, longer remissions, and fewer side effects.

Adolescent↗