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Biomedical subjects

K Sack

Publications and source records attributed to K Sack.

At least 91 records · Page 5Linked to original sources
PubMed1984

Renal tolerance and pharmacokinetics of vancomycin in rats.

The nephrotoxicity, as measured by urinary cell and enzyme excretion, of vancomycin was studied in rats. The lowest daily iv dose inducing significantly increased cell elimination was 25 mg/kg. Im administration caused less effects probably due to incomplete absorption from the im injection site, since im dosages of 100 mg/kg daily led to lower renal tissue concentrations than the same doses given iv. Nephrotoxicity of vancomycin increased when combined with tobramycin and was reduced when combined with D-glucaro-1.5-lactam, a beta-glucuronidase inhibitor. Vancomycin accumulated in renal tissue during repeated administration.

Animals↗
PubMed1983

[Serum gentamicin level after intratracheal application in ventilated patients with normal and reduced kidney function].

In a prospective study, serial serum determinations of gentamicin were made after its intratracheal application (40 mg/8 h) to 14 patients on ventilators (seven with normal renal function, seven with compensated, preterminal or dialysis-requiring renal failure). The patients with normal renal function had no therapeutic or toxicologically significant gentamicin concentration in their serum: less than 0.1 mg/l, in one case maximally 0.67 mg/l. But in patients with renal failure even the first gentamicin dose increased the serum level up to 1.5 mg/l. After repeated endotracheal application gentamicin accumulation in serum led to maximal values of 6.2 mg/l after the sixth and 7.5 mg/l after the seventh dose. The absorption of the drug from the tracheobronchial system differed between individuals. Thus serum concentrations were reached in patients with renal failure which are systemically effective and potentially toxic.

Adult↗
PubMed1983

[UV irradiation of the peritoneal dialysis solution for the prevention of peritonitis].

Micro-organisms causing peritonitis during peritoneal dialysis or CAPD can reach the peritoneal cavity either along the Tenckhoff-catheter or via contaminated dialysis fluid. Laboratory experiments with UV irradiation of artificially contaminated CAPD fluid were made to demonstrate whether decontamination could be achieved during the flow through a UV-penetrable (lambda 2537 A) section of the CAPD catheter. Five CAPD bags were contaminated with a fluid culture of the following micro-organisms which frequently cause peritonitis (S. epidermidis, S. aureus, P. aeruginosa, E. coli, and Candida albicans). After UV irradiation positive cultures could not be demonstrated. UV irradiation of the peritoneal dialysis fluid before entering the peritoneal cavity is proposed as an additional preventive measure.

Candida albicans↗
PubMed1983

Ceftazidime, ceftizoxime, cefotaxime and HR 221 in experimental chronic Escherichia coli pyelonephritis in rats.

The therapeutic efficacy and pharmacokinetics of the cephalosporins ceftazidime, ceftizoxime, cefotaxime and HR 221 were studied in animal experiments. The animal model used was experimental estrogen-induced or non-induced chronic Escherichia coli pyelonephritis in rats. The animals were treated with 5 mg cephalosporin/kg twice daily for one week. Each of the cephalosporins tested led to a significant decrease in renal bacterial counts, in spite of the low doses given. Ceftazidime was significantly more active than HR 221 in both experimental models, although the serum levels of HR 221 were higher and were maintained for a longer period of time than those of ceftazidime. Differences in pharmacokinetic properties (influenced by metabolic stability and protein binding) could be the reason for the differences in therapeutic activity, since the in vitro antimicrobial activity of each of the cephalosporins tested was very similar against the test strain.

Animals↗
PubMed1983

Ceftazidime in intensive care medicine and haemofiltration.

Twenty-seven intensive care patients with septicaemia or other infections and associated severe cardiovascular disease were treated with ceftazidime in a dose of 2 g iv twice daily. In 19 patients the infection was cured or improved during the therapy. Laboratory abnormalities were frequently seen but could in all cases be explained by severe underlying disease. Ceftazidime assays were performed in 6 patients with renal failure undergoing haemofiltration; 0.5 g ceftazidime given every second day maintained effective drug levels in these patients.

Bacterial Infections↗
PubMed1981

[Nephrotoxicity of cefsulodin: experimental studies in animals (author's transl)].

Experimental investigations in wistar rats indicate that cefsulodin, a new cephalosporin antibiotic with high activity against Pseudomonas aeruginosa, is more nephrotoxic than cephaloridine, the cephalosporin with the lowest renal tolerance up until new. Therefore, when cefsulodin is used clinically, renal function should be carefully controlled.

Animals↗
PubMed1981

[Animal experiments on the nephrotoxicity, pharmacokinetics and therapeutic efficacy of dibekacin].

Nephrotoxicity, pharmacokinetics, and therapeutic efficacy of 3',4'-dideoxykanamycin (dibekacin), a semisynthetic aminoglycoside, were evaluated in rats. As with other aminoglycosides, therapy with dibekacin led to an increased urinary cell and malic-dehydrogenase excretion. The lowest dose resulting in an increased urinary cell excretion was 2.5 mg/kg/d. Serum levels of dibekacin after i.m. injection of 5 mg/kg were similar to those of other aminoglycosides. The kidneys accumulated high amounts of dibekacin, and eliminated it with a half-life of about 7 days. After repetitive dosing a distinct tendency to accumulation (highest renal concentration: 330 microgram/g) could be detected. Experimental chemotherapy of the chronic estrogen induced pyelonephritis revealed that dibekacin and sisomicin fed to significant reductions of renal bacterial counts at a dosage of 2 x 5 mg/kg/d for 7 days. A dosage of 2 x 2.5 mg/kg/d diminished the effectiveness of dibekacin distinctly, that of sisomicin only slightly.

Animals↗
PubMed1981

[Animal studies on ribostamycin (author's transl)].

Nephrotoxicity, pharmacokinetics, and therapeutic efficacy of ribostamycin were evaluated in rats. Measures of nephrotoxicity were urinary excretion of tubular cells and malate dehydrogenase. The i.v. injections of ribostamycin lead to the same tubular cell excretion values as the i.m. injections. Parallel administration of D-glucaro-delta-lactam reduced the nephrotoxic effect of ribostamycin significantly. The lowest dose which leads to a significantly increased loss of tubular cells was 20 mg/kg/d and was distinctly above that of gentamicin, indicating a lower nephrotoxicity. This corresponded to lower renal ribostamycin concentrations after a single dose administration as well as after 9 times repeated dosing. In chemotherapy of the acute pyelonephritis of the rat ribostamycin was inferior to gentamicin at dosages of 2.5 or 5 mg/kg.

Animals↗
PubMed1980

Age-dependent nephrotoxicity and the pharmacokinetics of gentamicin in rats.

The pharmacokinetics and nephrotoxicity of gentamicin were studied in female Wistar rats of different ages. I.m. administration of 5 mg of gentamicin/kg revealed that young rats (90 g) had lower peak serum levels and a prolonged elimination half-life, when compared with adult animals. After repeated injections, renal gentamicin concentrations were continuously lower in young rats during the entire experiment until the 20th day after the last dose. Nephrotoxicity, as measured by urinary excretion rates of tubular cells and malic dehydrogenase, was most pronounced in the old rats (260 g) and distinctly less in the 210 g animals. The young rats reacted with a slight but not significant increase in cellular and enzyme excretion. Since one cause of nephrotoxicity can be assumed to be intrarenal accumulation of gentamicin, it may be concluded that a deficient ability to concentrate aminoglycosides in the kidneys resulted in decreased nephrotoxic potential of gentamicin in the young rats.

Age Factors↗
PubMed1980

[Experimental study on renal tolerability of aminoglycosides butirosin and bekanamycin (author's transl)].

The aminoglycosides butirosin and bekanamycin (Kanendomycin) were tested for their nephrotoxicity in female albino Wistar rats (n = 110). The antibiotics were administered i.m. over a course of 5 days; dosage interval 12 h, dosage 2,5, 5, 10, 20, 100 and 500 mg/kg per day, respectively. For comparative evaluation of nephrotoxicity the urinary excretion of tubular cells and enzymes (MDH, GOT, LDH) were taken. Additionally, serum urea and urine protein (qualitatively) were determined, and the kidneys were investigated histologically. The experiments revealed that both aminoglycosides had tubulotoxic and glomerulotoxic effects. The lowest doses that induced pathologic cell excretion (tubulotoxic threshold doses) were 5 mg/kg per day for either drug. It may be concluded that nephrotoxicity of butirosin and bekanamycin does not differ within the range of dosages which are used in human therapy. Compared with other established aminoglycosides advantages with respect to nephrotoxicity could not be found.

Animals↗
PubMed1980

[Experimental studies in animals on the nephrotoxicity of some new cephalosporin antibiotics: cefamandole, EMD 29 645, and 29 946 (author's transl)].

The cephalosporins cefamandole, EMD 29 645, and EMD 29 946 were tested for their nephrotoxicity in female albino Wistar rats (n = 120). The antibiotics were administered i.m. over a course of 5 days; dosage interval 12 h, dosages 1000, 2000, 3000, and 5000 mg/kg per day, respectively. For comparative evaluation of nephrotoxicity, the urinary excretion of tubular cells and enzymes (MDH, GOT, LDH) were taken. Additionally serum urea and urine protein (qualitatively) were determined. Furthermore the kidneys were investigated histologically. These experiments revealed the following tubulotoxic threshold doses: cefamandole: 3000 mg/kg per day, EMD 29 645: 2000 mg/kg per day, and EMD 29 946: 5000 mg/kg per day. EMD 29 645 was also found to be glomerulotoxic at higher doses.

Animals↗
PubMed1980

[Fosfomycin: animal experiments on nephrotoxicity, pharmacokinetics and therapeutic efficacy (author's transl)].

The nephrotoxicity, pharmacokinetic and therapeutic activity of fosfomycin were investigated in female wistar-rats. Measures of nephrotoxicity were urinary excretion of tubular cells and of the enzymes MDH, LDH, and GOT. Histological investigations and estimation of serum urea concentration and proteinuria were also evaluated. The doses of 500, 1000, 2000, 3000, and 5000 mg/kg/d were administered in 9 single doses with 12 hours interval. The lowest dose which induced a significantly increased tubular cell excretion was 1000 mg/kg/d and therefore in the same range as the tubulotoxic threshold doses of cephalosporins. Chemotherapy of the chronic estrogen induced pyelonephritis revealed equally favourable results for fosfomycin and cefuroxim at dosages of 2 X 150 mg/kg/d. The pharmacokinetics of fosfomycin at a single dose of 150 mg/kg/d were equivalent to those of cefuroxim. These animal experiments showed fosfomycin to be of value as a therapeutic alternative to cephalosporin antibiotics.

Animals↗
PubMed1979

Antimicrobial agents in rats. II. Serum levels of oral cephalosporins.

Cephalexin, cephradine and 7 beta-(D-2-amino-2-[(1,4-cyclohexadienyl)-acetamido])-3-methoxy-3-cephem-4-carboxylic acid (CGP 9000) were tested for their pharmacokinetic behaviour in rats. The cephalosporin serum concentrations were determined at certain times after oral administration of 150 mg/kg by the agar-well-diffusion method. The experiments revealed that the serum levels of cephalexin and cephradine did not differe essentially from one another. They maintained maximum serum concentrations of 30 microgram/ml to 40 microgram/ml during the first hour and than declined with a half-life of 2.5 h. CGP 9000 reached peak concentrations 60 to 90 min postdose and was eliminated with a half-life of 3.5 h. The area under the curve was double as large as those of cephalexin and cephradine. This may be a reason of favourable results in experimental chemotherapy with CGP 9000.

Animals↗
PubMed1979

Investigations on the effectiveness of cefazedone in experimental E. coli pyelonephritis.

The therapeutic effectiveness of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephazolin, cephacetrile and cephalothin was compared in the test model of estradiol-induced E. coli pyelonephritis in the rat. Cefazedone and cephazolin were similar in effect. The relations between results of treatment and microbiological and pharmacokinetic characteristics of the cephalosporins tested are discussed.

Animals↗