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Biomedical subjects

F F Horber

Publications and source records attributed to F F Horber.

63 records · Page 4Linked to original sources
PubMed1986

Pharmacokinetics of tenoxicam in patients with impaired renal function.

The pharmacokinetics of tenoxicam after a single oral dose of 20 mg has been studied in 12 patients with various degrees of decreased renal function. Unchanged tenoxicam and its 5'OH-metabolite in plasma and urine were determined by HPLC. The mean areas under the plasma concentration-time curve (138 +/- 53 micrograms/ml X h) and terminal half-lives in patients with impaired renal function did not differ from values previously reported in normal volunteers, nor did the peak concentration of tenoxicam. The half-life of 5'OH-tenoxicam and unchanged tenoxicam where the same. The urinary excretion of 5'OH-tenoxicam fell with decreasing renal function. Thus no dosage adjustment should be necessary and the usual daily dose of tenoxicam may be administered once daily also to patients with renal failure.

Adult↗
PubMed1986

Effect of liver function on the metabolism of prednisone and prednisolone in humans.

The systemic availability of total prednisone and unbound prednisolone, and the urinary excretion of 6 beta-hydroxyprednisolone, were measured after an oral dose of prednisone and an i.v. dose of prednisolone in 22 patients covering a wide range of liver function (galactose elimination capacity ranging from 3.3 mg/min X kg body wt to 9.2 mg/min X kg body wt). The area under the plasma concentration versus time curves of prednisolone and of prednisone decreased with increasing galactose elimination capacity. This dependency of the steroid concentrations on liver function was attributed to a decreased metabolic clearance and not to an increased systemic availability of the steroid given p.o. in patients with impaired liver function. The fractional excretion and the fractional clearance of 6 beta-hydroxyprednisolone declined with decreasing metabolic clearance rate of prednisolone or with decreasing galactose elimination capacity. Thus, the enzymes involved in the 6 beta-hydroxylation are not spared as liver function declines, and the exposure to the biologically active unbound prednisolone is increased in patients with impaired liver function in relation to the amount of prednisone or prednisolone administered.

Adult↗
PubMed1986

Altered skeletal muscle ultrastructure in renal transplant patients on prednisone.

Treatment with glucocorticoids causes wasting of proximal skeletal muscles. The purpose of the present investigation was to quantify in the thigh muscle the areas of the different fiber types determined by histochemical methods, and the muscle ultrastructure by means of electron microscopy, in normal subjects (N = 41) and in renal transplant patients treated with prednisone (N = 12). The cross-sectional area of all three fiber types was reduced in renal transplant patients treated with prednisone (10.6 +/- 4.3 mg/day), the fast glycolytic fibers being most affected (slow oxidative fibers: 2642 +/- 625 vs. 3677 +/- 970 micron2, P less than 0.001; fast oxidative fibers: 3275 +/- 735 vs. 4443 +/- 1343 micron2, P less than 0.01; fast glycolytic fibers: 2305 +/- 802 vs. 3920 +/- 1522 micron2, P less than 0.001). This was mostly due to a decrease in the volume of myofibrils per unit volume of muscle fiber (-30%). The intracellular lipid content and the volume density of subsarcolemmal mitochondria were increased by more than 70% in prednisone treated patients. In conclusion, the decreased myofibril areas might account for the muscle weakness in renal transplant patients treated with prednisone, and the decrease in myofibrils is in part functionally compensated by an increase in subsarcolemmal mitochondria and intracellular lipid content.

Adult↗
PubMed1986

Altered body fat distribution in patients with glucocorticoid treatment and in patients on long-term dialysis.

Fat distribution was assessed by computed tomography in normal volunteers (n = 42), patients on long-term dialysis (n = 18), and patients on glucocorticoids [renal transplant patients (n = 49), other diseases (n = 17)]. Patients on glucocorticoids had higher mediastinal (deep) and identical or increased posterior cervical, buccal, and midthigh (superficial) fat areas when compared with normal subjects. The pattern of fat distribution in dialysis patients mimicked the distribution observed in patients taking glucocorticoids. Healthy females had higher ratios of superficial to deep fat than healthy male subjects. Patients on prednisone or on dialysis lost this sex-associated difference in fat distribution. Since patients on prednisone exhibit increased or normal thigh fat depots in the presence of increased mediastinal fat, the current concept that glucocorticoids induce redistribution of body fat from peripheral to central fat compartments has to be revised. Furthermore, disease states and/or glucocorticoids abrogate sex-associated differences in body fat distribution.

Adipose Tissue↗
PubMed1986

Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin.

Amoxicillin and clavulanic acid are prescribed as a fixed drug combination. The purpose of the present study was to assess the influence of various degrees of renal insufficiency (glomerular filtration rate [GFR], less than 5 to greater than 75 ml/min per 1.73 m2) on the pharmacokinetics of amoxicillin and clavulanic acid following oral (500 and 125 mg of amoxicillin and clavulanic acid, respectively) and intravenous (1,000 and 200 mg, respectively) dosing. The volume of distribution and the systemic availability were independent of the renal function, while the total body clearance and the renal and the nonrenal clearance of amoxicillin and clavulanic acid decreased with decreasing renal function. The decrease in the total body clearance was more pronounced for amoxicillin than for clavulanic acid. This explains the increase in the ratio of the area under the plasma concentration versus time curve of amoxicillin to that of clavulanic acid with decreasing glomerular filtration rate after oral dosing; for example for a GFR of 75 ml/min, the ratio of amoxicillin to clavulanic acid was 4.9 +/- 1.2; for a GFR of 35 to 75 ml/min, 5.3 +/- 2.4; for a GFR of 10 to 35 ml/min, 11.9 +/- 5.8; for a GFR of 5 to 10 ml/min, 13.4 +/- 9.1; and for patients on hemodialysis, 14.7 +/- 5.3. Dosage recommendations are suggested which prevent undue accumulations of amoxicillin while maintaining adequate concentrations of clavulanic acid.

Amoxicillin↗
PubMed1985

Overestimation of renal function in glucocorticosteroid treated patients.

Creatinine clearance is commonly used as a parameter for individualization of dosages of drugs primarily excreted by the kidney. Nomograms and equations have been developed for estimating creatinine clearance from serum creatinine concentration, body weight, age and sex. Glucocorticosteroids are said to cause proximal muscle wasting and therefore may be expected to cause a decrease in the creatinine production rate. The purposes of the present investigation were first to evaluate by a computed tomography the effect of long term treatment with prednisone on the mid-thigh muscle area, and second, to establish whether the presumed supposed decrease in muscle mass was associated with a decrease in the urinary creatinine excretion rate, and hence in a systematic error whenever a nomogram is used to predict creatinine clearance in such subjects. Patients taking prednisone had smaller mid-thigh muscle areas than controls. A linear relationship between the mid-thigh muscle area and the observed urinary excretion of creatinine was found, suggesting that the muscle loss could account for the decrease in the urinary excretion rate of creatinine. The ratio of observed to predicted (by nomogram) urinary creatinine excretion was lower in patients than controls, resulting in a corresponding underprediction of creatinine clearance by nomograms in the patients taking prednisone.

Adult↗
PubMed1985

Thigh muscle mass and function in patients treated with glucocorticoids.

Treatment with glucocorticoids causes wasting of proximal skeletal muscles. There is evidence that physical training improves muscle mass and strength in glucocorticoid-treated rats. Whether this is also true in humans is unknown. The present investigation was designed to establish in what respect moderate physical training may alter muscle mass and function as assessed quantitatively by computed tomography (CT) and with an isokinetic dynamometer (Cybex II). Compared with matched controls, both female (n = 17) and male (n = 22) patients treated with prednisone (15.4 +/- 6.6 mg die-1) had a lower mid-thigh muscle area of 20 and 45% and an increased mid-thigh fat/muscle ratio of 25 and 100%, respectively. The mean peak torque and the total work output of the thigh muscle were lower by 20-30% (n = 14). Fifty days of isokinetic training in six patients increased the thigh muscle area, decreased the thigh fat area and normalized the mean peak torque and total work output. Thus, glucocorticoid-induced muscle wasting can be reversed by increasing physical activity.

Adult↗
PubMed1985

Evidence that prednisone-induced myopathy is reversed by physical training.

Treatment with glucocorticoids causes wasting of proximal skeletal muscles. There is evidence that physical training improves muscle mass and strength in glucocorticoid-treated rats. Whether this is also true in humans is not known. The present investigation was designed to establish in what respect moderate physical training may alter muscle mass and function as assessed quantitatively by computed tomography (CT) and an isokinetic dynamometer (Cybex II). Compared with matched normal subjects (n = 12), patients (n = 12) treated with prednisone [12.6 +/- 3.3 (+/- SD) mg/day] had a 20% lower midthigh muscle area and a 36% increase in midthigh fat to muscle ratio. The mean peak torque and the total work output of the thigh muscle were lower by more than 20%. Baseline measurements of total work output or peak torque at all tested velocities increased with midthigh muscle area (r = 0.73; n = 24; P less than 0.001). Fifty days of isokinetic training in 12 patients increased the thigh muscle area, decreased the thigh fat area, and normalized the mean peak torque and total work output. The increase in peak torque was inversely correlated with the daily dose of prednisone (r = 0.60; n = 12; P less than 0.05). Thus, glucocorticoid-induced muscle wasting can be reversed by increasing physical activity in patients taking a low to moderate dose of prednisone.

Adult↗