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Biomedical subjects

D Höffler

Publications and source records attributed to D Höffler.

At least 37 records · Page 2Linked to original sources
PubMed1987

Pharmacokinetics of ofloxacin in healthy subjects and patients with impaired renal function.

Ten healthy volunteers and 20 patients suffering from chronic renal failure of varying severity received a single dose of ofloxacin 200mg orally. Ofloxacin concentrations were determined in blood and urine, and kidney function was assessed by measuring glomerular filtration rate (GFR) and plasma creatinine concentrations. The results show that there is a relationship between the area under the concentration-time curve for ofloxacin and both GFR and plasma creatinine concentration. On the basis of these results, a means of determining suitable dosage reduction factors in patients with renal impairment is presented. It is anticipated that appropriate reductions in the amount of ofloxacin administered to such patients will reduce the risk of central nervous system side effects.

Adult↗
PubMed1987

Pharmacokinetics and dose recommendations of carumonam in renal failure.

The pharmacokinetics of (Z)-[[[(2-aminothiazol-4-yl)[[(2S,3S)-2-(hydroxymethyl)-4-oxo-1- sulfoazetidin-3-yl]carbamoyl]methylene]amino]oxo]acetic acid, disodium salt (carumonam, Ro 17-2301) after a 2 g intravenous infusion (20 min) were evaluated in 10 healthy volunteers and 20 patients with various degrees of renal failure. The main results of the kinetic parameters in healthy volunteers (mean + SD) corrected for zero infusion time and 70 kg body weight were: t1/2 alpha, 29 +/- 12 min; t1/2 beta, 108 +/- 27 min; AUCtot, 327 +/- 40 mg h/l; Vdss, 12.2 +/- 1.5 l/70 kg; urinary recovery, 78.7 +/- 8.2%; total clearance 103 +/- 13 ml/min; renal clearance, 85 +/- 13 ml/min. Because of the large variation in the degree of renal insufficiency, calculations of the mean values for the pharmacokinetic parameters in the patient group were not generally justified with the exception of the volume of distribution (Vdss = 14.4 +/- 3.0 l/70 kg). To derive dose recommendations, a regression analysis was performed using values from both the volunteer and patient group for the total area under curve (AUCtot) and glomerular filtration rate (GFR), divided by the mean AUCtot value for the volunteers. This curve can be interpreted as giving the dose reduction factor (DRF) as a function of GFR, where by definition, DRF = 1 for healthy (and young) subjects. Using this method of equivalent areas, no (or only a slight) dose reduction is necessary for patients with GFR values above 40 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Pharmacokinetic studies on clavulanate potentiated ticarcillin in normal subjects and patients with renal insufficiency.

Pharmacokinetics of the novel combination of ticarcillin with the beta-lactamase inhibitor clavulanic acid (BRL 28500, Timentin, Betabactyl) was investigated in order to calculate the dose reduction factor (DRF) and elaborate dosage recommendations for patients with varying degrees of renal impairment. Serum and urine levels of ticarcillin and clavulanic acid have been determined following the i.v. application of 3.2 g and 5.2 g BRL 28500 consisting of 3.0 g and 5.0 g ticarcillin, respectively, and 0.2 g of clavulanic acid each. 10 healthy volunteers and 9 patients received the 5.2 g formulation, and 6 normal subjects and 9 patients the 3.2 g formulation. The pharmacokinetics of both components of BRL 28500 behave fairly similarly and provides the combination with a logic basis. The dose reduction factor, being 1 by definition in normal renal function, rises in final renal failure to 2-3 for clavulanic acid and to 4-5 for ticarcillin. A dosis reduction to 1/2-1/4 will roughly produce the same AUC in a patient with terminal renal insufficiency as the normal dosage in a healthy subject. The distribution volume of ticarcillin and clavulanic acid was found to be enlarged probably due to overhydration in this group of patients. The recovery of both BRL 28500 components decreased with impaired renal function. The recovery 6 h after administration of 0.2 g clavulanic acid in the 5.2 g (3.2 g) BRL 28500 formulation fell from 58 +/- 12% (52 +/- 6) in healthy subjects to 25 +/- 14% (25 +/- 13) in patients with renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Clavulanic Acids↗
PubMed1985

Tolerance in patients with terminal renal insufficiency of high doses of cefotaxime.

Eleven patients with terminal renal insufficiency requiring dialysis were treated with 3 X 2 g cefotaxime in an open study lasting five days when the clinical findings strongly indicated a serious bacterial infection. The effect of the administration of the high-dose antibiotic on the coagulation system (Quick test, partial thromboplastin time, thrombin time, antithrombin III and platelets) and on brain function (EEG) was investigated. The serum levels showed that the serum concentrations were not abnormally high in cases of terminal renal insufficiency requiring dialysis. In contrast to previous investigations in other beta-lactam antibiotics, no changes in the coagulation system or EEG occurred. On the basis of these findings, no reduction in the dose appears necessary for cefotaxime, if therapy does not exceed five days.

Adult↗
PubMed1985

Temocillin pharmacokinetics in normal and impaired renal function.

In 18 healthy volunteers and 18 patients with varying degrees of impaired renal function, the plasma concentrations after intravenous administration of temocillin 0.5, 1, and 2g were determined. Another group of 6 patients received temocillin 0.5 g intramuscularly. Surprisingly, it was found that with higher doses, the plasma concentrations, and consequently the area under the plasma concentration/time curve (AUC), did not increase proportionately. Instead, the renal and, to a greater extent, the total clearance of temocillin increased. The plasma concentrations in patients with impaired renal function were clearly higher than in the subjects with normal renal function. Dose-reduction factors were derived which allowed the determination of the dosing regimen necessary to achieve approximately the same high plasma concentrations (and the same AUCs) in patients with impaired renal function as in healthy subjects. However, these dose-reduction factors could only be determined for certain doses because of the specific behaviour of temocillin.

Glomerular Filtration Rate↗
PubMed1984

Dose- and sex-independent disposition of ciprofloxacin.

Serum concentrations and urinary excretion of ciprofloxacin were studied in female and male volunteers following a single oral administration of 100 mg, 250 mg, 500 mg or 1000 mg. Serum and urine concentrations increased proportionally to the increasing dose administered but independently of sex. Twenty-five percent of the administered dose was excreted in the urine as unmetabolized ciprofloxacin within the first 24 hours after oral administration. Renal clearance averaged 5 ml/min X kg.

Adult↗
PubMed1984

Nitrendipine in hypertension that is difficult to control.

Fifty-five patients suffering from essential or renal hypertension who had been insufficiently treated previously with combination therapy using diuretics and beta-blockers as well as reserpine, clonidine, prazosin, captopril, or minoxidil have been included in this open study. In addition to receiving diuretics and beta-blockers alone or in combination with reserpine, clonidine, or methyldopa, the patients were given nitrendipine in a dose of 2 X 20 to 2 X 40 mg/day. A normalisation of blood pressure values was attained in 46 of the 55 patients; 18 of these patients have been treated for more than 1 year. Few side-effects were observed. Dizziness and ankle oedema each occurred once. A rash occurred in one patient, causing the withdrawal of nitrendipine. No complaints of headache and palpitations were made. It may be concluded that nitrendipine is well suited as a partner in the combination treatment of patients with essential or renal hypertension that is difficult to stabilise.

Adrenergic beta-Antagonists↗
PubMed1984

Pharmacokinetics of ceftazidime in normal and impaired renal function.

The concentration of ceftazidime in serum and urine was measured after 2 g i.v. in 10 healthy volunteers and 19 patients with various degrees of renal insufficiency. Elimination observed in normal volunteers can best be described by a two-compartment model. In renal insufficiency elimination of ceftazidime is markedly diminished, resulting in a larger area under the serum level curve (area under the curve; AUC). AUC and glomerular filtration rate (as well as AUC and plasma creatinine) can be brought into a mathematical relation. From these relations a dose reduction factor (DRF) can be derived. By means of this factor a dose can be calculated for each degree of renal impairment which causes the same AUC that would be anticipated in a subject with normal renal function. Dose recommendations in tabular form are presented. The urinary recovery decreases with impaired renal function; nevertheless therapeutical urine levels are observed down to dialysed patients.

Ceftazidime↗
PubMed1984

On the pharmacokinetics of latamoxef in normal and impaired renal function.

Pharmacokinetics of latamoxef (Moxalactam) have been investigated in 10 normal volunteers and 20 patients with impaired renal function after i.v. injection of 2 g. Elimination observed in normal volunteers can best be described by a two-compartment model. In the presence of impaired renal function elimination of latamoxef is markedly prolonged. The result is a larger area under the serum level curve (area under the curve; AUC). AUC and glomerular filtration rate (as well as AUC and plasma creatinine as approximate measure of renal function) can be brought into a mathematical relation. From these relations a dose reduction factor (DRF) can be derived. By means of this factor a dose can be calculated for each arbitrary degree of renal impairment which causes the same AUC that would be anticipated in a subject with normal renal function. Dosing proposals are given in tabular form. These allow to bring about, that in each conceivable degree of renal failure, an AUC would be reached as it would have been attained in normal subjects.

Creatinine↗
PubMed1983

The pharmacokinetics of ceftazidime in normal and impaired renal function.

The concentration of ceftazidime in serum and urine was measured in ten healthy volunteers and 19 patients with renal impairment following a 2 g iv dose of ceftazidime. In impaired renal function the elimination rate of ceftazidime is decreased considerably, whereupon the area under the curve (AUC) rises sharply. Dose reduction factors (DRF) for several degrees of renal function are presented. The urinary recovery decreases with renal function; but therapeutic urine levels can still be detected in patients on dialysis. Patients with renal insufficiency should be given reduced dosage according to a dose reduction factor and according to the table.

Ceftazidime↗
PubMed1983

Pharmacokinetics of Cefmenoxime in normal and impaired renal function.

7 beta-[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido]-3-[(1- methyl-1H-tetrazol-5-yl)thiomethyl]-ceph-3-em-4-carboxylic acid hemihydrochloride (Cefmenoxime), a new cephalosporin with a broad spectrum of activity against gram-positive and gram-negative bacteria, was investigated pharmacokinetically. 10 healthy volunteers and 20 patients with renal disease each received 2 g of the substance i.v. The plasma levels were monitored for 6 h in healthy volunteers and for 24 h in the patients with renal disease. The analysis of the data showed that the majority of the curves could be properly evaluated only with the aid of a two-compartment model. Therefore a simple half-life cannot be given. Cefmenoxime is eliminated more rapidly than cefoperazone, but more slowly than cefotaxime. The area under the serum level curves (AUC) increases when renal function is impaired. There is a mathematical correlation between the AUC and the renal function parameters, plasma creatinine and glomerular filtration rate. This gives the dose reduction factors, allowing the calculation of the doses with the same AUC on restricted renal function as that observed in healthy persons after normal doses. Dosage recommendations are given in the form of tables regarding the questions 1. to what extent the dose may be reduced in impaired renal function without lowering the AUC and 2. what is the highest safe dose.

Cefmenoxime↗