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Biomedical subjects

D Höffler

Publications and source records attributed to D Höffler.

At least 73 records · Page 4Linked to original sources

Pharmacokinetics of amikacin for treatment of urinary tract infections in patients with reduced renal function.

Amikacin (250 mg four times daily for 10 days) was administered intramuscularly to 22 patients with long-standing, severe infections of the urinary tract, in each case superimposed on chronic uropathy or nephropathy. Therapy with amikacin was completely successful in 14 patients (sterile 14-day follow-up urine specimens obtained by suprapubic needle aspiration of the bladder) and partially successful in three (sterile three-day but positive 14-day follow-up urine specimens). Five patients were judged to be treatment failures. Quantitative assessment of pyuria revealed a significant drop in the rate of excretion of white cells to near normal levels not only in patients who were cured but also in others, a finding which suggests that the infectious process had been affected by amikacin in all cases. The course of the disease in individual patients suggested that amikacin therapy can be successful after a long series of failures from treatment of such conditions with other antibiotics. Additional pharmacokinetic studies indicated that the half-life of amikacin may be increased five- to 10-fold in patients with renal insufficiency. A tentative dosage schedule was prepared for patients with various degrees of impaired renal function on the basis of average half-life values.

Aged↗

[Influence of diazepam and phenytoin on penicillin-induced cerebral convulsions (author's transl)].

The effects of diazepam and phenytoin on penicillin-induced EEG changes and convulsions were studied in 32 rabbits. EEG changes and convulsions were elicited by 2.4 g/kg benzylpenicillin i.v. over 50 min. The dosages of the anticonvulsants were 1, 5 and 10 mg of diazepam and 10, 20 and 30 mg/kg of phenytoin. The qualitative and semiquantitative evaluation of the electroencephalograms revealed no reduction of spike frequency or spike amplitude for either of the two drugs. However, in contrast to phenytoin, diazepam was highly effective in preventing the development of generalized convulsions. None of the 12 diazepam-treated animals developed a convulsion, whereas in most of the phenytoin treated animals and in most of the controls generalized convulsions appeared. The results suggest that diazepam should be used in the treatment of penicillin-encephalopathy.

Animals↗

[Pharmacokinetics of intravenous Cefradin in normal and restricted renal function (author's transl)].

Half life and distribution volume of Cefradin were investigated in 22 patients with various degrees of renal function in which Cefradin was indicated and set in relation to glomerular filtration (determined by the 51Cr EDTA method). An average distribution volume of 21.8 +/- 3.5% of the body weight was found and a correlation between the half life of Cefradin and the glomerular filtration in the form of a power function. Estimations of levels were made from the pharmacokinetic data (half life, distribution volume) which serve as a basis for the recommendation of isoconcentration dosages. These are graduated according to the different degrees of renal insufficiency and given in tabular form for single injections and for continuous infusion drip therapy.

Adult↗

[Dosage and elimination of Dextran 40 in patients on hemodialysis (author's transl)].

In 24 patients on regular hemodialysis the serum levels and the half-life of dextran 40 were determined after single or repeated infusion of dextran 40 (Rheomacrodex¿). One group of hemodialysis trainees had a dextran 40 half-life of 2237 +/- 447 min. In contrast, a second group, consisting of hospital dialysis patients, had a dextran 40 half-life of 4283 +/- 510 min, whereas patients with normal renal function had a half-life of 573 +/- 183 min. The difference in dextran half-life between the two groups of hemodialysis patients may be explained by the better residual renal function of our hemodialysis trainees. During hemodialysis no change in serum dextran levels could be observed. Intermitten hemodialysis, also, had no influence on the exponential elimination of dextran over a period of 6.25 days. Since hemodialysis by itself has no effect upon dextran elimination, the dosage fo dextran 40 has to be adjucted to the prolonged elimination time only, disregarding dialysis. After the fourth infusion of 50 g dextran 40 (twice a week 500 ml of 10% dextran 40) serum dextran levels exceeding 50 g/l and cutaneous bleeding were observed. To avoid these complications an initial saturation dose is suggested, followed by a maintenance dose adjusted to the impaired renal function.

Arteriovenous Shunt, Surgical↗

Cerebral toxicity of penicillins in relation to their hydrophobic character.

The neurotoxic effects of ticarcillin, methicillin, phenthicillin, oxacillin, cloxacillin and dicloxacillin were studied in the conscious rabbit. During and after intravenous administration of 1.2 and 2.4 g/kg, resp., over 50 min the blood concentrations of the drugs were determined and the neurotoxicity assessed by continuous recording of the electroencephalogram. The hydrophobia of the penicillins was characterized by determination of their partition coefficients between isobutanol and buffer solution pH 7.4. The penicillins showed quite different neurotoxic properties. A close correlation (r = 0.928) was found between the neurotoxic potency of the penicillins and their partition coefficients. With increasing hydrophobia the neurotoxic potency increased in the following sequence: Ticarcillin, methicillin, oxacillin, phenethicillin, cloxacillin, dicloxacillin. It can be concluded, therefore, that determination of the partition coefficient of a penicillin gives valuable information on the neurotoxicity to be expected. The introduction of a neurotoxicity quotient revealed that penicillins may be divided into two groups: less neurotoxic penicillins with a partition coefficient below 1.0 and highly neurotoxic penicillins with a partition coefficient above 1.0.

Animals↗