Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PREDNISOLONE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1984

Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans.

Following induction of the microsomal liver enzymes, lower total prednisolone concentrations in plasma and an altered pattern of the prednisolone metabolites generated were observed. The purpose of the present study was to establish whether--as a consequence of an enhanced clearance--lower unbound concentrations of prednisolone in plasma are detectable after enzyme induction and to determine if the altered prednisolone metabolism modulates the biological effect. Before and during phenytoin dosage in ten volunteers, the mean (+/-SD) total body clearance (ml min-1 kg-1) of both total and unbound prednisolone increased from 2.74 +/- 0.47 to 3.94 +/- 0.66 (P less than 0.001) and from 10.76 +/- 2.68 to 16.00 +/- 3.17 (P less than 0.001), respectively. These increments were due to increased non-renal clearances. The immunosuppressive activity as a function of time in plasma determined as the percent inhibition of the mixed lymphocyte reaction decreased by one third after phenytoin dosing, while the EC50 values of unbound prednisolone were unaffected. Thus enzyme induction decreases both the unbound prednisolone concentration and the steroid efficacy.

Adult↗
PubMed2003

Prednisolone 21-sulfate sodium: a colon-specific pro-drug of prednisolone.

Prednisolone 21-sulfate sodium (PDS) was synthesized as a colon-specific pro-drug of prednisolone with the expectation that it would be stable and non-absorbable in the upper intestine and release prednisolone by the action of sulfatase once it was delivered to the colon. In-vitro/in-vivo properties were investigated using rats as test animals. PDS was chemically stable at pH 1.2, 4.5, 6.8 and 8.0, and the apparent partition coefficient was 0.11 in 1-octanol/pH 6.8 buffer solution at 37 degrees C. PDS was stable on incubation with the contents of the stomach or small intestine. When PDS (0.1 mg equiv. of prednisolone) was incubated with the caecal contents (0.05 g), prednisolone was produced to a maximum 54% of the dose in 6 h and decreased thereafter, which suggested that reduction of the A ring took place in addition to the hydrolysis by sulfatase. After oral administration of PDS, a small portion of prednisolone was recovered from the cecal contents but not from the small intestine. Neither PDS nor prednisolone was detected in the plasma, suggesting that absorption of PDS is limited. The data demonstrate that the sulfate ester can serve as a novel colon-specific pro-moiety by limiting the absorption of the pro-drug in the upper intestine and releasing the active compound by the action of microbial sulfatase in the colon.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of prednisolone after high doses of prednisolone hemisuccinate.

Prednisolone in the form of its hemisuccinate was given intravenously in two different doses (1200 mg and 75 mg). Plasma levels of the ester and prednisolone were measured and pharmacokinetic parameters were calculated. The results indicate a dose-dependency in the pharmacokinetics of both hemisuccinate and the free alcohol. For the high dose 8 per cent of the administered ester was found unchanged in the urine indicating incomplete conversion of the pro-drug. Comparison with previous studies leads to the conclusion that prednisolone shows doubled non-linear pharmacokinetics with higher total body clearance in the medium dose range than in the low and high dose range. Volume of distribution changes accordingly, but overall elimination rate remains remarkably constant. Saliva levels of prednisolone were low and agree reasonably well with calculated plasma concentrations of free, non-protein-bound prednisolone. No prednisolone hemisuccinate was found in saliva.

Adult↗
PubMed1982

In vitro studies into the release of chlorhexidine acetate, prednisolone sodium phosphate, and prednisolone alcohol from cold cure denture base acrylic.

An investigation was carried out into the release of chlorhexidine acetate, prednisolone sodium phosphate, and prednisolone alcohol from a cold cured acrylic denture base material. The drugs were added at 10% w/w with the powder phase of the material. Water, at the concentrations of 10%, 20%, and 30% of the monomer phase of the material was added to chlorhexidine-containing and chlorhexidine-free samples. Spectrophotometric and bioassay measurements of the release of chlorhexidine demonstrated protracted delivery to 140 days. The daily release rate was increased by the addition of water to the material and at 30% water incorporation the release was greater and increased up to 190 days. The release pattern of prednisolone sodium phosphate was similar to that of chlorhexidine without the addition of water. Prednisolone alcohol was released for a much shorter period and at lower levels. Scanning electron microscopic examination of the polished, etched, and fractured surfaces of the material demonstrated that chlorhexidine acetate and prednisolone sodium phosphate were incorporated into the interbead matrix areas of the material. The irregularities in the material increased with the addition of water. Prednisolone alcohol produced minimal changes in the specimens except after soaking in water for 140 days when numerous small defects could be seen in the matrix zones at high magnification. The use of materials such as water to increase porosity appears a simple method of improving the release pattern of drugs from acrylic. However, the strength of the resulting material would require support from an existing intraoral prosthesis or appliance.

Acrylic Resins↗
PubMed1976

Comparative serum prednisone and prednisolone concentrations following prednisone or prednisolone administration to beagle dogs.

The relative serum prednisone and prednisolone concentrations were determined following the administration of prednisone or prednisolone as 5-mg tablets to male beagle dogs. Serum prednisone concentrations were significantly greater following prednisone administration than they were following prednisolone administration. Serum prednisolone concentrations were significantly greater following treatment with prednisolone than with prednisone. The combined prednisone and prednisolone areas under the serum concentration-time curves were similar for the two treatments.

Animals↗
PubMed1995

Simultaneous determination of prednisolone, prednisolone acetate and hydrocortisone in human serum by high-performance liquid chromatography.

A method for the simultaneous determination of prednisolone, prednisolone acetate and hydrocortisone has been established to monitor the serum levels of these three compounds in healthy volunteers following intramuscular administration of prednisolone acetate. Serum samples of 0.75 ml were extracted with ethyl acetate after addition of the internal standard, dexamethasone. The compounds were separated using a LiChrosorb Si 60 column and detected by UV absorbance. Specificity, linearity, as well as the repeatability, intermediate-precision and accuracy of the method were established. The lower limit of quantification was 20 ng/ml for prednisolone (C.V. = 14.7%, n = 6) and 5.0 ng/ml for prednisolone acetate (C.V. = 13.9%, n = 6) and hydrocortisone (C.V. = 11.7%, n = 6). Data on the recovery of the compounds and the internal standard are provided. The results of quality control samples determined during routine analysis (n = 114) are presented. Serum levels of the compounds after intramuscular administration of 25 mg of prednisolone acetate are discussed.

Chromatography, High Pressure Liquid↗
PubMed2004

Clinical outcomes in a randomized controlled study comparing azathioprine and prednisolone versus prednisolone alone in the treatment of severe leprosy type 1 reactions in Nepal.

The ILEP nerve function impairment and reaction research programme (INFIR 2) was a group of clinical trials conducted to identify second-line treatments for severe leprosy type 1 reactions (T1R). This paper presents the clinical results of one of these trials in which azathioprine was used in combination with short-course prednisolone to ascertain if the combination was effective in controlling the symptoms and signs of reaction. Forty patients were alternately assigned to a 12-week treatment with either AP (12 weeks azathioprine at 3mg/kg/d plus 8 week reducing course prednisolone starting at 40mg/d) or P (12-week reducing course prednisolone starting at 40mg/d). Evaluation included serial quantitative clinical assessments. The overall frequency of side effects was similar in both groups. Results show that there was no difference in clinical outcome in the AP and P groups and a similar number of patients in each group required extra prednisolone for worsening clinical features. We conclude that a 12-week course of azathioprine at 3mg/kg/day plus an 8 week reducing course of prednisolone starting at 40mg/d is as effective as a 12 week reducing course of prednisolone starting at 40mg/d and that the combination therapy is well-tolerated in severe leprosy T1R patients.

Administration, Oral↗
PubMed1993

Prednisolone stimulates hepatic glutathione synthesis in mice. Protection by prednisolone against acetaminophen hepatotoxicity in vivo.

Mediators of inflammation modulate the extent of hepatocellular necrosis following the administration of hepatotoxins. Since corticosteroids interfere with the generation of some of these mediators they might thus protect against the hepatotoxicity of drugs such as acetaminophen. To test this hypothesis mice were pretreated with two doses of prednisolone (10 and 20 mg/kg i.p., 17 and 2 h, respectively) prior to a hepatotoxic dose of 375 mg/kg acetaminophen and the metabolism and toxicity of acetaminophen were assessed. Twenty-four hours after acetaminophen the activity of ALT in plasma (737 vs. 6775 U/l) and the extent of hepatocellular necrosis (4 vs. 45% necrotic hepatocytes) were significantly lower in prednisolone-pretreated mice. Prednisolone pretreatment resulted in decreased covalent binding of the toxic metabolite in vivo and an increased urinary excretion of glutathione-derived conjugates of acetaminophen, indicating an enhanced detoxification of the reactive metabolite by glutathione. Nevertheless, hepatic glutathione was less depleted by acetaminophen in the prednisolone group, indicating an increased capacity to resynthesize glutathione. This was confirmed in experiments with diethyl maleate which depletes hepatic glutathione without causing cell injury. Following the administration of diethyl maleate to fed and fasted mice, hepatic glutathione was depleted to the same extent after 45 min, but was significantly higher after 2.5 h in prednisolone-pretreated mice. The present results indicate that prednisolone increases the capacity to replete depleted hepatic glutathione stores in mice.

Acetaminophen↗
PubMed2005

Continuous prednisolone versus conventional prednisolone with VMCP-interferon-alpha2b as first-line chemotherapy in elderly patients with multiple myeloma.

We report on a randomised trial that aimed to compare the efficacy of continued daily prednisolone treatment during the entire induction phase, with prednisolone given for 2 weeks of each cycle in combination with VMCP (vincristine, melphalan, cyclophosphamide, prednisolone)-interferon-alpha 2b (IFN-alpha 2b) treatment in 299 previously untreated elderly patients (median age: 67 years) with multiple myeloma. After completion of induction treatment patients were randomised to IFN-alpha 2b with or without prednisolone, thrice weekly. Response rate was 62% in the continuous and 60% in the control arm (intent to treat analysis, P=0.81). Progression-free survival [median: 20 months vs. 19 months; hazard ratio (HR): 0.99, 95% confidence interval (CI): 0.74-1.33, P=0.97] and overall survival (median: 34 months vs. 37 months; HR: 1.16, 95% CI: 0.85-1.59, P=0.35) were similar in both groups. Reduced performance status (Eastern Cooperative Oncology Group, grades 2-4) was the predominant risk factor for poor survival followed by age >65 years, high beta2-microglobulin, and impaired renal function. There was more grades 3-4 dyspnoea and cardiac impairment and grades 1-2 hyperglycaemia, but less nausea, emesis and anaemia in patients on continuous prednisolone therapy. In conclusion, continuing prednisolone treatment during the entire duration of the induction phase with VMCP-IFN-alpha 2b did not improve outcome.

Adult↗
PubMed1990

Stability of prednisolone and prednisolone acetate in various vehicles used in semi-solid topical preparations.

The stability of prednisolone and prednisolone acetate has been investigated at 37 degrees C in seven semi-solid vehicles, including almond oil, beeswax, Cremophor RH 40, Lanette N, and hydrogel formulations of hydroxy-propylcellulose, carbomer and bentonite. Extraction methods and a high-performance liquid chromatographic (HPLC) procedure have been developed in order to assay the content of undegraded steroid at time 0 and after 28 days. Prednisolone acetate showed superior stability compared to prednisolone. Bentonite induced considerable degradation of both steroid compounds, whereas the two absorption bases, Cremophor RH 40 and Lanette N, affected mainly the stability of prednisolone. In the carbomer hydrogel, prednisolone acetate hydrolysed to a small extent during the trituration process. The most effective steroid stability was found in the two lipophilic bases and the hydroxypropylcellulose hydrogel.

Administration, Topical↗
PubMed1976

Plasma prednisolone levels after administration of prednisolone-21-phosphate as a retention enema in colitis.

A competitive protein-binding assay was used to measure plasma prednisolone levels after administration of prednisolone-21-phosphate retention enemas to seven patients with colitis. Prednisolone appeared in the plasma of all patients after the enema, and concentrations rose to a peak within three hours. In five of the patients plasma prednisolone levels were also measured after the same dose of prednisolone by mouth. Although in individual patients the plasma levels achieved by enema were often quite different from those achieved by mouth, overall the levels achieved by each mode of administration were of a similar order. These findings suggest that 20 mg prednisolone given by retention enema may well exert a systemic effect.

Adult↗
PubMed1981

Serum prednisolone levels in Crohn's disease and coeliac disease following oral prednisolone administration.

Serum prednisolone levels have been measured following the oral administration of 20 mg prednisolone in 10 normal subjects, in 9 patients with Crohn's disease and in 6 with coeliac disease. Serum prednisolone levels showed more variation in patients with Crohn's disease when compared to normal subjects. In those patients with Crohn's disease who failed to respond to corticosteroid therapy, adequate serum levels of prednisolone were achieved. Patients with coeliac disease had levels similar to normal. Serum protein binding of prednisolone was not significantly different between the groups. We conclude that, even in the presence of mucosal damage, patients with coeliac disease and Crohn's disease achieve therapeutic serum prednisolone levels.

Administration, Oral↗
PubMed1979

Studies comparing the metabolic clearance rate of 11 beta,17,21-trihydroxypregn-1,4-diene-3,20-dione (prednisolone) after oral 17,21-dihydroxypregn-1,4-diene-3,11,20-trione and intravenous prednisolone.

The MCR of prednisolone (11 beta,17,21-trihydroxypregn-1,4-diene-3,20-dione) and the absorption of prednisone (17,21-dihydroxypregn 1,4-diene-3,11,20-trione) were studied in five normal subjects and four patients. Plasma and urinary prednisolone were measured by a competitive radioassay. The MCR was determined after iv administration of 30 mg nonisotopic prednisolone using one-compartment (MCR1) and two-compartment (MCR2) analyses. These values were compared with the MCR determined after oral administration of nonisotopic prednisone (MCR0). MCR1 and MCR2 were closely correlated, indicating the applicability of first order kinetics to the study of prednisolone metabolism. In subjects with normal gastrointestinal function, MCR0 was consistently lower than MCR2 (mean MCR2 = 0.175 liters/h.kg; MCR0 = 0.145 liters/h.kg). In two patients with steroid malabsorption, the MCR0 was significantly greater than MCR2. Knowledge of the expected relationship between MCR0 and MCR2 allowed quantitation of the degree of malabsorption. With or without impaired absorption, the absorptive process was essentially complete by the time of the peak plasma concentration. Estrogen therapy lowered the MCR0, and high prednisone dose increased the MCR0. Those effects and the effects of iv prednisolone administration on the MCR are explained by the effects of plasma protein binding of prednisolone. These studies demonstrate the usefulness of the oral MCR determination in the evaluation of steroid absorption and metabolism.

Administration, Oral↗
PubMed1985

Comparative carcinogenic activity of prednimustine, chlorambucil, prednisolone and chlorambucil plus prednisolone in Sprague-Dawley rats.

This study compares long term toxic effects of equivalent doses of prednimustine (12 mg/kg) chlorambucil (3 mg/kg), prednisolone (3 mg/kg) and chlorambucil plus prednisolone (3 mg/kg each) in comparison to vehicle treated controls after regular administration over a period of 18 months to 600 female Sprague Dawley rats. Frequency of administration to subgroups (30 rats each) varied between 9 (a), 4.5 (b), 2 (c) times or once (d) a month. When comparing organ specific, age-adjusted expected versus observed incidences after natural death of animals an increased tumor risk was found in organ systems of all treatment modalities but prednisolone. Prednimustine-administration was related to an elevated risk of developing squamous-cell carcinomas of the external auditory canal only (alpha = 0.013), whereas simultaneous application of chlorambucil plus prednisolone induced significantly higher rates of adenocarcinomas of the mammary gland, of malignant tumors of the central and peripheral nervous tissue and of squamous cell carcinomas of the external auditory canal (alpha less than 0.01 for each tissue). Chlorambucil alone caused a significantly higher rate of malignancies of the hematopoietic and lymphatic tissue (alpha less than 0.01) additionally to effects observed after the unlinked mixture of chlorambucil plus prednisolone. There is evidence of carcinogenic activity of prednimustine compared to untreated controls, but the cancer-inducing potential of the linked compound is distinctly lower than that of the unlinked mixture of chlorambucil plus prednisolone or of chlorambucilalone.

Animals↗
PubMed1993

Deposition of ciprofloxacin, prednisolone phosphate, and prednisolone acetate in SeeQuence disposable contact lenses.

We noted opaque deposits in SeeQuence disposable contact lenses in three patients with persistent epithelial defects who were being treated with topical ciprofloxacin and prednisolone acetate. In each patient, the contact lenses with deposits were removed and replaced. High performance liquid chromatography analysis revealed the deposits to be precipitates of ciprofloxacin and prednisolone acetate. We incubated new SeeQuence disposable contact lenses in ciprofloxacin, prednisolone phosphate, and prednisolone acetate alone and in combination. Precipitates did form when ciprofloxacin was combined with either prednisolone acetate or prednisolone phosphate. We recommend removal and replacement of contact lenses should these deposits develop to prevent the possibility of corneal toxicity.

Aged↗
PubMed1987

Lymphotoxic activity of methyl prednisolone in vitro--I. Comparative toxicity of methyl prednisolone in human cell lines of B and T origin.

The cytotoxic activity of methyl prednisolone was compared in EB-3(B), NALM-6(B), CCRF-CEM(T) and RPMI-8226 (plasma cell) cell lines derived from human lymphoid malignancies. Whereas EB-3 cells were steroid-sensitive, NALM-6 cells were partially sensitive and CCRF-CEM and RPMI-8226 were steroid resistant at concentrations of methyl prednisolone up to 10(-4) M. A high concentration of methyl prednisolone, 2.5 X 10(-3) M was toxic to all cell lines. Steroid-sensitivity did not correlate with the incorporation of [3H] dexamethasone and could not be mimicked by flurbiprofen, a non-steroidal anti-inflammatory agent. Both theophylline and di-butyryl cAMP were toxic towards NALM-6, EB-3 and CCRF-CEM cells; however, this toxicity was reversible and did not reflect the cells' sensitivities towards methyl prednisolone. Furthermore, elevated levels of cAMP in theophylline-treated cells, were not demonstrable in cells treated with methyl prednisolone at toxic or non-toxic concentrations of the steroid. Steroid-sensitive EB-3 cells exposed to 10(-5) M methyl prednisolone, produced a soluble factor which was toxic CCRF-CEM cells.

B-Lymphocytes↗
PubMedDate not supplied

The nonlinear pharmacokinetics of prednisone and prednisolone. II. Plasma protein binding of prednisone and prednisolone in rabbit and human plasma.

The protein binding characteristics of prednisone and prednisolone were determined in human and rabbit plasma and in a 4.7 per cent human serum albumin (HSA) solution. The influence of prednisolone on prednisone binding in human plasma was also examined. Prednisolone exhibited nonlinear binding and prednisone linear binding characteristics in both human and rabbit plasma. Prednisone binding was not influenced by the presence of prednisolone. Prednisone binding to HSA was linear but to a degree substantially lower than observed in human plasma, suggesting the possibility that prednisone binds to other proteins in human plasma. The results support the hypothesis that the protein binding characteristics of prednisone and prednisolone do not explain the reported nonlinear pharmacokinetics of prednisone.

Animals↗
PubMed1979

Variation in plasma prednisolone concentrations in renal transplant recipients given enteric-coated prednisolone.

Renal transplant recipients receiving intermittent haemodialysis and kept under normal ward conditions showed appreciable differences in plasma prednisolone concentrations after therapeutic doses of enteric-coated prednisolone tablets. This gross day-to-day variation occurred irrespective of the dosage used. Breakfast given before prednisolone tended to reduce the rate of absorption of the drug, the effect being quantitatively most pronounced with large doses. Haemodialysis had no apparent effect on the elimination of prednisolone from plasma. Such erratic blood concentrations of prednisolone as observed in these patients, possibly resulting from variable absorption, may be potentially hazardous. Hence use of enteric-coated tablets in renal transplant recipients should be viewed with caution.

Adolescent↗