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Biomedical subjects

F J Frey

Publications and source records attributed to F J Frey.

At least 163 records · Page 9Linked to original sources
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

Prednisolone pharmacodynamics assessed by inhibition of the mixed lymphocyte reaction.

Eight to 14 plasma samples were obtained from 12 patients on chronic prednisone treatment following their usual dose of prednisone (0.262 to 1.053 mg/kg . day) and following an equivalent amount of prednisolone given i.v. Total and unbound prednisolone were assessed by high performance liquid chromatography and by equilibrium dialysis. The immunosuppressive activity of the plasma was determined as the inhibition of the mixed lymphocyte reaction. The area under the plasma concentration time curve (AUC) for total and unbound prednisolone and the area under the inhibition time curve (AUIC) of the mixed lymphocyte reaction were determined by the trapezoidal rule. A hyperbolic concentration response curve was found when inhibition of the mixed lymphocyte reaction was plotted versus concentrations of total and free prednisolone. The mean EC50 (+/- SD) for total prednisolone concentration following the oral and the i.v. dosing was 66.3 +/- 26.7 and 86.5 +/- 30.9 ng/ml, respectively; for free prednisolone concentration the corresponding values were 10.0 +/- 5.0 and 12.4 +/- 12.6 ng/ml. A similar hyperbolic relationship is observed when the AUIC is plotted versus the AUC of free or total prednisolone, but not when AUIC is plotted versus the oral dose. Over the range of drug concentrations observed, no difference is found between total and free concentrations in the ability to predict inhibition of the mixed lymphocyte reaction.

Binding, Competitive↗
PubMed1982

Inequality of clearance values obtained by intravenous bolus and by steady-state infusion. Prednisolone studies in dogs.

In order to compare total and free prednisolone clearance values following an intravenous bolus dose with those following zero-order infusions to steady state, 6 dogs were given an intravenous bolus and four different zero-order infusions of prednisolone. Prednisolone clearance for the infusion studies were calculated by dividing the infusion rate by the steady-state concentration. Time-averaged clearances for the intravenous bolus doses were calculated as dose divided by area under the concentration curve. The total and unbound prednisolone clearance values calculated using the steady-state levels averaged 24 and 39% higher, respectively, than the corresponding clearance values obtained following intravenous bolus dosing.

Animals↗
PubMed1982

Altered prednisolone kinetics in patients with the nephrotic syndrome.

The impact of low plasma protein levels on the kinetics of prednisolone was investigated in patients with the nephrotic syndrome. Nephrotics exhibited higher unbound fractions of prednisolone, lower total plasma concentrations than normal volunteers, but normal unbound plasma concentrations and normal mean residence times. Thus altered prednisolone kinetics in patients with low plasma protein levels do not explain the higher frequency of prednisolone-related side-effects in these patients, compared to patients with normal plasma protein levels.

Adult↗
PubMed1982

Endogenous and exogenous glucocorticoids in cushingoid patients.

The pharmacokinetics of prednisone/prednisolone and the time-course of endogenous hydrocortisone were investigated in 15 stable renal transplant patients and 12 patients with oral mucocutaneous vesiculoerosive diseases. All 27 patients were given their usual prednisone dose orally on one occasion, and 24 were given an equivalent amount of prednisolone intravenously on another occasion. After dosing, 8-14 plasma samples were obtained for the determination of total prednisolone, prednisone, and hydrocortisone concentrations by high performance liquid chromatography and unbound prednisolone concentrations by equilibrium dialysis. The bioavailability of prednisone, the interconversion of prednisone into prednisolone, the total and unbound prednisolone clearances, the prednisolone binding capacity of albumin and transcortin, and the affinity of albumin for prednisolone were not different when the 14 patients without cushingoid side effects were compared with the 13 cushingoid patients. Patients with cushingoid side effects had a higher affinity constant for prednisolone binding to transcortin, more frequently exhibited peak hydrocortisone levels within the normal range, and more often had measurable (greater than 10 ng/ml) hydrocortisone in the plasma samples collected during the kinetic studies, as compared with those not showing side effects. The data suggest that endogenous hydrocortisone production is not as suppressed in patients with visible cushingoid signs as in noncushingoid patients and that no significant difference in the pharmacokinetics of exogenous glucocorticoids exists between patients with and without cushingoid side effects.

Blood Proteins↗
PubMed1982

Prednisolone clearance at steady state in man.

The present study was undertaken to determine whether prednisolone exhibits dose-dependent kinetics in man. Ten normal volunteers were infused to steady state over a 7-h period at a low (5.5 microgram/h . kg) and a high (64 microgram/h . kg) rate with prednisolone. Steady state prednisolone levels differed by a factor of 5 [91 +/- 25 and 437 +/- 116 ng/ml (mean +/- SD)] when the infusion rate was increased 12-fold, indicating a marked increase in the clearance of total prednisolone with increasing dose (the ratio of clearances, high to low dose, was 2.47 +/- 0.29). The fraction of unbound prednisolone increased from 0.12 +/- 0.02 to 0.24 +/- 0.02 with increasing dose. Since the increase in the free fraction (2-fold change) was not as great as the increase in the total prednisolone clearance, there was a slight but significant (P less than 0.05) increase in the apparent clearance of unbound prednisolone (ratio of apparent unbound clearances, high to low dose, was 1.29 +/- 0.24). The interconversion between prednisolone and prednisone appears to approach a maximum prednisone concentration, as was noted previously by us in dogs. In humans, we found this maximum prednisone concentration to be 52 ng/ml when prednisolone is infused. Therefore, the ratio of concentrations, prednisolone to prednisone, also increased with increasing prednisolone dose. These results indicate that prednisolone exhibits dose- and concentration-dependent kinetics and that the great majority of the change in kinetics may be attributed to saturable protein binding of prednisolone. Although there is an increase in the apparent clearance of unbound prednisolone with increasing concentrations, these results are confounded by the interconversion process between prednisone and prednisolone.

Adult↗
PubMed1982

Three radioactivity detectors for liquid-chromatographic systems compared.

Three radioactivity detectors coupled to a "high-performance" liquid-chromatography system are compared with regard to static efficiency, dynamic efficiency, background measurements, and within- and between-day variabilities. Their advantages and disadvantages are discussed.

Chromatography, High Pressure Liquid↗
PubMed1981

A single dose of azathioprine does not affect the pharmacokinetics of prednisolone following oral prednisone.

Clinical and pharmacokinetic observations suggest that azathioprine may diminish the plasma level of prednisolone. To study the extent of this possible interaction, and to define the underlying mechanism, total and unbound prednisolone and total prednisolone concentrations were assessed in 11 subjects following an oral dose of prednisone once with and once without concomitant oral administration of azathioprine. Azathioprine did not affect the area under the plasma concentration-time curve of total and unbound prednisolone; furthermore, the interconversion of prednisone into prednisolone was not influenced by azathioprine.

Administration, Oral↗
PubMed1981

Endogenous hydrocortisone, a possible factor contributing to the genesis of cushingoid habitus in patients on prednisone.

To establish if the cushingoid habitus in patients taking prednisone is associated with relatively high total or free prednisolone and low endogenous hydrocortisone concentrations in plasma, 15 stable renal transplant patients and 12 patients treated with prednisone for oral mucocutaneous vesiculo-erosive diseases were investigated. After the patients' usual prednisone doses, the areas under the plasma concentration time curve of total and free prednisolone were not different when the 14 patients without cushingoid appearance were compared to the 13 patients with cushingoid appearance. Patients with cushingoid habitus more frequently exhibited peak hydrocortisone levels within the normal range (6 of 14 vs. 1 of 13) and had higher areas under the plasma concentration time curve of hydrocortisone (median, range), i.e. 2672 ng/ml.min (0-21, 637 ng/ml.min) vs. 308 ng/ml.min (0-12, 495 ng/ml.min) compared to those without cushingoid appearance (P less than 0.05). These results indicate that pharmacokinetic differences of prednisone do not explain the presence or absence of cushingoid habitus and that there is an association between cushingoid habitus and endogenous hydrocortisone levels.

Adult↗
PubMed1980

Prediction of the histological type of glomerulonephritis. Multiple discriminant analysis of clinical and laboratory characteristics at time of diagnosis.

We performed a prospective study on 68 subjects with biopsy-proven clomerulonephritis using a discriminant analysis of 12 clinical and laboratory characteristics. Among these, the selectivity of proteinuria, the presence of hematuria and the plasma level of C3 proved to be the most useful. An equation based on these three variables discriminated without overlap between 17 patients with minimal change glomerulonephritis (MCGN) and 30 patients with either membranoproliferative or rapidly progressive glomerulonephritis. However, some overlap existed between MCGN and focal sclerosis or membranous glomerulonephritis. In addition, the formula seems to identify steroid-resistant patients with MCGN.

Adolescent↗
PubMed1980

Prednisolone clearance at steady state in dogs.

The purposes of this study were: 1) to determine in dogs under steady-state conditions whether prednisolone clearance increases with increasing dose as has been suggested from results obtained under nonsteady-state conditions in man and 2) to determine whether the prednisolone to prednisone conversion, apparently resulting from 11 beta-hydroxydehydrogenase, is saturable. Six dogs were given four different zero-order infusions of prednisolone resulting in steady-state levels from 23 to 5884 ng/ml.Prednisone, total and free prednisolone levels were assessed by high-pressure liquid chromatography and equilibrium dialysis. Total and unbound prednisolone clearances were calculated by dividing the infusion rate by the total or unbound prednisolone concentration at steady state. Both total and unbound prednisolone clearance exhibited a slight tendency to decrease (P < .05) with increasing prednisolone steady-state levels. The conversion of prednisolone to prednisone, defined by the prednisolone/prednisone ratio, exhibited saturable characteristics which, when data for all dogs was fitted to a Michaelis-Menten type equation (r2 = 0.938), gave a Km of 658 ng/ml, i.e., total prednisolone concentration at half-maximal saturation.

Animals↗
PubMed1979

Selectivity as a clue to diagnosis of postural proteinuria.

In 14 patients with fixed and reproducible postural proteinuria and 14 patients with histologically proven glomerulonephritis, the selectivity of proteinuria was measured separately in the day and night urine collections. The selectivity of proteinuria in the urine collected in recumbency was lower in patients with glomerulonephritis than in patients with postural proteinuria. All patients with postural proteinuria showed an increment of the selectivity from day to night of at least 13 degrees, whereas the maximum increment in patients with glomerulonephritis was 5 degrees. The changes in selectivity from day to night in patients with postural proteinuria and patients with glomerulonephritis were significantly different and seem to be a useful discriminatory test.

Adolescent↗
PubMed1979

Liquid-chromatographic measurement of endogenous and exogenous glucocorticoids in plasma.

The therapeutic response to and side effects of glucocorticoids will be better recognized and the recovery of the adrenals during the tapering of therapy with steroids better evaluated if endogenous and exogenous glucocorticoids are separately assessed. We describe a specific method for simultaneously measuring the concentrations of cortisone, cortisol, prednisone, and prednisolone in plasma by "high-pressure" liquid chromatography. The steroids, together with an internal standard, dexamethasone, are extracted from 1 mL of plasma with methylene chloride-ether, washed with acid and base, and separated isocratically on a normal-phase silica column with a mobile phase consisting of methylene chloride/tetrahydrofuran/methanol/glacial acetic acid (96.85/1/2.1/0.05 by vol) at a flow rate of 1.3 mL/min. The steroids are detected at 254 nm and quantitated by peak-height measurements; their retention times range from 6 to 20 min. The lower limits for routine detection of all four compounds is 10 microgram/L. The analytical recoveries are about 75%; the intra-day variability (CV) is 1 to 9%, and the inter-day variability 2 to 11%. Of 26 drugs and 20 steroids tested, only theophylline presents an interference problem.

Chromatography, High Pressure Liquid↗
PubMed1977

[Serum lipids in diminished kidney function, during hemodialysis and after kidney transplantation].

Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27).

Adult↗