Biomedical subjects

U F Legler

Publications and source records attributed to U F Legler.

28 records · Page 2Linked to original sources

PubMed1988

Impairment of prednisolone disposition in patients with Graves' disease taking methimazole.

This study was undertaken to determine the effect of methimazole on the pharmacokinetics of iv prednisolone in patients with Graves' disease. Twenty women were studied, including eight with severe infiltrative ophthalmopathy who had taken methimazole and T4 for at least 4 months, six with severe infiltrative ophthalmopathy who had undergone subtotal thyroidectomy and, therefore, required no antithyroid treatment, and six age-matched normal women. All were euthyroid. Each women received 0.54 mg/kg prednisolone as an iv bolus dose. Plasma total and unbound prednisolone concentrations were measured at multiple times during a 10-h study period by high pressure liquid chromatography and equilibrium dialysis. The clearance of both total and unbound prednisolone was increased significantly in the women receiving methimazole therapy compared to values in both control groups. The volume of distribution at steady state was similar in all groups. These results suggest that patients receiving methimazole have enhanced prednisolone metabolism and, therefore, they may require higher prednisolone doses.

Adult↗

PubMed1988

Pharmacokinetics of cloprednol in healthy volunteers.

Kinetic data for the synthetic corticoid cloprednol were determined in 8 healthy male volunteers after single oral doses (20 mg). Maximal plasma levels (Cmax) of 426 +/- 116 ng/ml occurred within 101 +/- 44 min after oral intake. Cloprednol plasma levels declined monoexponentially after oral administration. Total apparent plasma clearance was 4.07 +/- 0.72 ml/min/kg and apparent clearance of unbound cloprednol was 9.75 +/- 0.8 ml/min/kg. Plasma protein binding was 74 to 94%. Volume of distribution at steady-state was 0.81 +/- 0.14 l/kg for total cloprednol and 1.99 +/- 0.33 l/kg for unbound drug. The results presented in this study characterize the kinetics of total and unbound cloprednol for the first time.

Administration, Oral↗

PubMed1987

Enhanced prednisolone elimination: a possible cause for failure of glucocorticoid therapy in Graves' ophthalmopathy.

This study was undertaken to determine the pharmacokinetics of intravenous prednisolone in patients with Graves' eye disease. 6 women with Graves' ophthalmopathy treated with prednisolone for severe endocrine exophthalmos were compared with 6 healthy female volunteers. All subjects with Graves' disease had been taking carbimazole and I-thyroxine as concurrent drugs for at least 4 months prior to study day. All subjects were euthyroid. Each subject received .54 mg/kg prednisolone as an i.v. bolus. Plasma concentrations for total and unbound prednisolone were determined by HPLC and equilibrium dialysis. Significant increase (p less than .01) in clearance values and significant decreases in half-life times (p less than .01) were found for both total and unbound prednisolone in women with Graves' disease compared with the control subjects. Volumes of distribution at steady-state were unchanged in both groups. The data suggest that patients with Graves' ophthalmopathy show an enhanced elimination for prednisolone and that is why they may need higher doses of corticoid although the function of the thyroid gland is euthyroid.

Adult↗

PubMed1987

5-Fluorocytosine kinetics in patients with acute renal failure undergoing continuous hemofiltration.

The pharmacokinetic disposition of 5-fluorocytosine (5-FC) was studied in 7 patients with acute renal failure undergoing continuous hemofiltration (CH). CH was performed with a high-flux membrane and the average filtration rate (FR) was 16.3 ml/min. Following an intravenous loading dose of 2,500 mg, 5-FC concentrations were measured in plasma and ultrafiltrate. The half-lives of 5-FC were markedly prolonged in all patients, ranging from 15.9 to 37.2 h and longer half-lives corresponded to lower FR. The clearance of 5-FC averaged 97.5% of the FR. Within 48 h, 29-35% of the administered dose was recovered in the ultrafiltrate of 3 patients. The volume of distribution ranged from 0.772 to 0.982 l/kg. We found a linear relationship between the elimination rate constant and the FR, and based on these data, a dosage schedule is proposed regarding the use of 5-FC in patients treated with CH.

Acute Kidney Injury↗

PubMed1986

Pharmacokinetics of fluocortolone in man.

The kinetics of the synthetic corticoid fluocortolone was determined in 9 healthy female volunteers after a single oral dose of 20 mg. The maximal plasma level fluocortolone (Cmax) of 202 +/- 70 ng/ml occurred within 85 +/- 32 min of oral intake after which it declined monoexponentially. Total plasma clearance was 6.48 +/- 2.07 ml/min X kg and the clearance of unbound fluocortolone was 60.38 +/- 26.67 ml/min X kg. Plasma protein binding was 83 to 95%. The volume of distribution at steady-state was 1.01 +/- 0.341/kg for total fluocortolone and 11.21 +/- 3.771/kg for unbound drug. The results of the study characterize the kinetics of unbound fluocortolone for the first time. In addition, the kinetics of total fluocortolone presented here confirm values calculated previously.

Adult↗

PubMed1986

The effect of prednisone and hydrocortisone on the plasma protein binding of prednisolone in man.

The protein binding of prednisolone was studied in plasma obtained from healthy volunteers in the presence of added amounts of prednisone and hydrocortisone. The plasma protein binding was determined using in vitro equilibrium dialysis for 16 h at 37 degrees C against isotonic Krebs-Ringer buffer using radioactive prednisolone. Prednisone appeared to have no effect on prednisolone binding. This surprising result was observed even when prednisone concentrations were more than 35 fold greater than prednisolone concentrations. In contrast, a marked competition between hydrocortisone and prednisolone was observed. These binding data were fit using a nonlinear least squares regression computer program and the capacity and affinity constants for the binding of prednisolone to transcortin and albumin were estimated including the competition for binding sites between prednisolone and hydrocortisone. The results from these studies compare favorably with recent parameter calculations, and our previous work where differences in binding were noted between cushingoid and noncushingoid patients.

Blood Proteins↗

PubMed1986

Marked alterations in dose-dependent prednisolone kinetics in women taking oral contraceptives.

Six healthy women chronically (greater than 6 months) using oral contraceptives were age- and weight-matched with female controls. Each subject received prednisolone, 0.53 and 0.14 mg/kg iv. In the subjects taking oral contraceptives there were significant decreases in total clearance, unbound clearance, and volume of distribution at steady state for total drug, and significant increases in total and unbound prednisolone t1/2 and hydrocortisone concentrations compared with control subjects at both the high and low prednisolone doses. Both the oral contraceptive group and the control group had significantly higher total clearance, volume of distribution for total drug, and unbound fraction for the high dose compared with the low dose. Data suggest that chronic low-dose contraceptive steroid use results in a marked decrease in prednisolone clearance; however, dose-dependent changes in kinetics are still observed.

Adult↗

PubMed1986

Impairment of prednisolone disposition in women taking oral contraceptives or conjugated estrogens.

Companion studies were designed to determine the effects of oral contraceptives and conjugated estrogens on the pharmacokinetics of prednisolone. Twenty-four normal women entered the studies, including six young women taking oral contraceptives and six age-matched control women, and six postmenopausal women receiving conjugated estrogens and six age-matched postmenopausal women. All received 0.53 mg/kg prednisolone phosphate, iv. Significant decreases (P less than 0.05) in the clearance and volume of distribution and significant increases in the half-life were found for both total and unbound prednisolone in the women taking oral contraceptives compared to values in the young control women. A significant decrease in the unbound clearance and increases in the total and unbound half-lives of prednisolone were found in the women receiving conjugated estrogens compared to values in the postmenopausal control women. Total clearance and volume of distribution were unchanged by conjugated estrogen therapy. Administration of prednisolone to women receiving estrogen-containing oral contraceptives or conjugated estrogens results in exposure of these women to increased concentrations of unbound prednisolone for increased periods of time. Increases in the pharmacological and toxic effects of prednisolone might be expected in these women.

Adult↗

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↗

PubMedDate not supplied

Posterior capsule opacification.

A complication of extracapsular cataract extraction with or without posterior chamber intraocular lens (PC-IOL) implantation is posterior capsule opacification. This condition is usually secondary to a proliferation and migration of residual lens epithelial cells. Opacification may be reduced by atraumatic surgery and thorough cortical clean-up. Clinical, pathological and experimental studies have shown that use of hydrodissection, the continuous curvilinear capsulorhexis and specific IOL designs may help reduce the incidence of this complication. Capsular-fixated, one-piece all-polymethylmethacrylate PC-IOLs with a C-shaped loop configuration and a posterior convexity of the optic are effective. Polymethylmethacrylate loops that retain "memory" create a symmetric, radial stretch on the posterior capsule after in-the-bag placement, leading to a more complete contact between the posterior surface of the IOL optic and the taut capsule. This may help form a barrier against central migration of epithelial cells into the visual axis. Various pharmacological and immunological methods are being investigated but conclusive data on these modalities are not yet available.

Cataract↗