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Journal of Pharmacobio-dynamics Dec 1982We studied the mechanism on protective effect of fosfomycin against experimental nephrotoxicity induced by dibekacin. In order to simplify an experimental model, the...
We studied the mechanism on protective effect of fosfomycin against experimental nephrotoxicity induced by dibekacin. In order to simplify an experimental model, the dehydrated Wistar rats were used, because a single injection of dibekacin at 30 mg/kg induced acute renal failure in the dehydrated rats, characterized by alteration of urinalytic parameters and BUN values, and retarded elimination of dibekacin from blood. When the rats were administered simultaneously with fosfomycin at 120 mg/kg, the rate of elimination was restored almost to normal, accompanied with improvement of the nephrotoxic parameters. However, markedly accelerated elimination over normal one was not observed, indicating that the improved elimination was not the reason of protection but a result of normal kidney function. On the other hand, fosfomycin protected the proximal tubular lysosomes from the injury of aminoglycoside, as evidenced a) in vivo by suppression of myeloid body formation and protection of lysosomal membrane integrity of the rats treated with dibekacin, and b) in vitro by dose-dependent protection of the lysosomal membrane integrity of the kidney cells. A study of structure-protective activity relation revealed that phosphonate anion possessing an epoxy function was important for protection, and that the mechanism of protection differed from the antibacterial mechanism.
Topics: Animals; Anti-Bacterial Agents; Dehydration; Dibekacin; Fosfomycin; In Vitro Techniques; Kanamycin; Kidney; Kinetics; Lysosomes; Male; Rats; Rats, Inbred Strains
PubMed: 7169607
DOI: 10.1248/bpb1978.5.941 -
Antimicrobial Agents and Chemotherapy Sep 1980The pharmacokinetics of dibekacin, a new aminoglycoside antibiotic, was studied in volunteers given the same dose (100 mg) intramuscularly on two separate occasions and...
The pharmacokinetics of dibekacin, a new aminoglycoside antibiotic, was studied in volunteers given the same dose (100 mg) intramuscularly on two separate occasions and intravenously at two different rates of infusion. The kinetic parameters (t 1/2, 2.24 h, and Vd, 0.136 liter/kg, as the overall mean) observed after intramuscular administration appear to be compatible with those of other aminoglycosides and fairly reproducible within the same individuals. Dibekacin was rapidly absorbed (tmax, 0.84 h), yielding a peak level of 10.4 microgram/ml after the 100-mg intramuscular dose. After the 30- or 60-min infusion, the concentrations of dibekacin in serum fell bi-exponentially, giving an elimination half-life (t 1/2 beta) of 2.50 to 2.88 h. The highest serum levels after th 30- and 60-min infusions were 15.2 +/- 0.9 and 12.1 +/- 1.8 microgram/ml, respectively. Serum levels at 6 h after completion of infusions were 1.9 +/- 0.3 and 1.7 +/- 0.4 microgram/ml, respectively.
Topics: Adult; Bacillus subtilis; Dibekacin; Humans; Injections, Intramuscular; Injections, Intravenous; Kanamycin; Kinetics; Male; Middle Aged
PubMed: 6775594
DOI: 10.1128/AAC.18.3.372 -
La Nouvelle Presse Medicale Nov 1982The study of the bronchial concentration of dibekacin has shown a different degree of activity than that of gentamicin. This activity resembles that of amikacin with a...
The study of the bronchial concentration of dibekacin has shown a different degree of activity than that of gentamicin. This activity resembles that of amikacin with a three hour time lag from the appearance of the bronchial peak in relationship to the serum peak. In addition there seems to be a special passage mechanism for the antibiotic from the blood into the bronchial secretions since we observed an increase in the mucus/serum ratio through time.
Topics: Adult; Aged; Bronchi; Dibekacin; Humans; Kanamycin; Kinetics; Middle Aged; Mucus; Respiratory Tract Infections
PubMed: 7155857
DOI: No ID Found -
Journal of Pharmacobio-dynamics Sep 1982Protection by fosfomycin of the nephrotoxicity of dibekacin was studied using Fischer 344 rats and urinary parameters such as volume, osmolality, protein,...
Protection by fosfomycin of the nephrotoxicity of dibekacin was studied using Fischer 344 rats and urinary parameters such as volume, osmolality, protein, N-acetyl-beta-D-glucosaminidase, leucine aminopeptidase, lactate dehydrogenase and nucleated cells were determined as markers of nephrotoxicity. The duration of treatment was 11 d. Fosfomycin reduced polyuria, proteinuria, enzymuria and cyturia induced by dibekacin best by the concomitant administration, followed by pre-treatment, but not by post-treatment. Protection was effective in the dose ratio of dibekacin: fosfomycin = 1:2 - 1:32, regardless of administration routes. As judged from urinalysis, protection by fosfomycin (320 mg/kg) was almost complete for the experimental nephrotoxicity induced by 10 mg/kg of dibekacin, and still significant for that by 40 mg/kg. This was supported by the histo-pathological and ultrastructural improvement of proximal tubules and by suppressed blood urea nitrogen and creatinine values. Protective activity of fosfomycin was more potent than that of cephalothin, when compared on the weight basis.
Topics: Animals; Anti-Bacterial Agents; Cephalothin; Chemical Phenomena; Chemistry; Dibekacin; Dose-Response Relationship, Drug; Fosfomycin; Kanamycin; Kidney Diseases; Male; Rats; Rats, Inbred F344; Time Factors
PubMed: 7153839
DOI: 10.1248/bpb1978.5.659 -
The Journal of Antibiotics Mar 1984A study was made of the serum levels and of the pharmacokinetic parameters of dibekacin after administration by intravenous infusion at a dose of 2 mg/kg of the drug to...
A study was made of the serum levels and of the pharmacokinetic parameters of dibekacin after administration by intravenous infusion at a dose of 2 mg/kg of the drug to rabbits using different infusion times. The peak serum level (Cmax) was seen to decrease progressively on increasing infusion time. The maximum value of Cmax was obtained after administration of the antibiotic by single bolus injection with an average value of 18.297 +/- 9.694 micrograms/ml, while the minimum value was obtained after intravenous infusion over 1 hour, with an average value of 6.597 +/- 1.250 micrograms/ml. A series of linear relationships was established between different pharmacokinetic parameters and the infusion time and a decrease was observed in the pharmacokinetic parameters alpha, K12, K21 and K13 when the infusion time was increased. Changes were also observed in the distribution kinetics of dibekacin in the rabbit on varying the infusion conditions, suggesting alterations in the access and permanence of the antibiotic in tissues.
Topics: Animals; Dibekacin; Infusions, Parenteral; Kanamycin; Kinetics; Male; Models, Biological; Rabbits; Time Factors
PubMed: 6725142
DOI: 10.7164/antibiotics.37.285 -
The Journal of Antimicrobial... Jan 1986The in-vitro inactivation kinetics of dibekacin by three semi-synthetic penicillins (carbenicillin, ampicillin and ticarcillin) were studied taking into account the...
The in-vitro inactivation kinetics of dibekacin by three semi-synthetic penicillins (carbenicillin, ampicillin and ticarcillin) were studied taking into account the influence of certain factors such as time, the concentration of the semi-synthetic penicillin in the sample and the reaction medium used in the inactivation process. For a dibekacin/beta lactam concentration ratio of 1/100, the maximum percentage of inactivation of dibekacin was obtained for ticarcillin (99%), followed by carbenicillin (90%) and finally by ampicillin (65%) over a period of 45 h. For carbenicillin and ampicillin a linear relationship was established between the inactivation constant (Ki) and the concentration of these penicillins in the sample. It was also found that under the same experimental conditions the inactivation percentage in human serum was smaller than that observed in buffered solution, pH = 7.4. It was observed that the degree of inactivation of dibekacin and gentamicin was similar under the experimental conditions employed in this study.
Topics: Ampicillin; Carbenicillin; Chemical Phenomena; Chemistry; Dibekacin; Drug Interactions; Humans; Kanamycin; Kinetics; Penicillins; Ticarcillin
PubMed: 3949639
DOI: 10.1093/jac/17.1.83 -
The Journal of Antibiotics Jun 2015
Comparative Study
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Design; Escherichia coli; Gentamicins; Kanamycin; Microbial Sensitivity Tests; Molecular Structure; Pseudomonas aeruginosa; Solubility; Staphylococcus aureus
PubMed: 25712399
DOI: 10.1038/ja.2015.6 -
Yakugaku Zasshi : Journal of the... Jun 2007Aminoglycosides are mainly distributed in the extracellular fluid, so when they are given to neonates who have a large amount of extracellular fluid, their distribution... (Review)
Review
Aminoglycosides are mainly distributed in the extracellular fluid, so when they are given to neonates who have a large amount of extracellular fluid, their distribution is increased. In our data, the volume of distribution (Vd) of Arbekacin in the neonates was twice that of the adults, 0.54 l/kg. Therefore, the dose per weight of aminoglycosides to the neonates should be increased more than to the adults. In the renal function of the neonates, differentiation of the nephron is completed within 36 weeks after conception, but it is functionally immature. In our data, renal drug excretion increased rapidly in the post-conceptional ages (PCAs) of 34-35 weeks. Consequently, we based the Arbekacin administration schedule for the neonates on the PCAs. There is excellent correlation between serum level of vancomicin (VCM) and dose x serum creatinine (Scr)/weight in the haemodialysis patients, suggesting that we can use weight and Scr to set the VCM administration schedule for these patients. We also established on administration schedule of Teicoplanin for the haemodialysis patients. In this article, we present the TDM analysis result of the antibiotics in our hospital.
Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Body Weight; Dibekacin; Drug Administration Schedule; Drug Monitoring; Extracellular Fluid; Humans; Infant, Newborn; Kidney; Patient Care Team; Renal Dialysis; Renal Insufficiency; Teicoplanin; Vancomycin
PubMed: 17541241
DOI: 10.1248/yakushi.127.925 -
Pathologie-biologie May 1984Levels of an aminoglycoside, dibekacin, are studied in bone. Fifteen specimens were obtained by Tanzer trocar biopsy three hours after the ninth injection of dibekacin...
Levels of an aminoglycoside, dibekacin, are studied in bone. Fifteen specimens were obtained by Tanzer trocar biopsy three hours after the ninth injection of dibekacin (1 mg/kg). Separation of cortical and spongy bone was not feasible owing to the small weight of specimens. Dibekacin concentrations were determined by microbiological assay. These concentrations were evaluated using a reference range in bone tissue determined with the same method and must be corrected according to blood levels. Dibekacin levels were 0.22 +/- 0.10 mg/l in healthy, non- contaminated specimens, and 1.70 and 1.80 mg/l in infected bone tissue.
Topics: Bacterial Infections; Bone Diseases; Bone and Bones; Dibekacin; Humans; Kanamycin; Kinetics
PubMed: 6739143
DOI: No ID Found -
Journal of Pharmaceutical and... 1986An immunoassay based on fluorescence polarization detection (FPIA) has been recently adapted for dibekacin. This has been compared with a reference method...
Dibekacin assay in serum by automated fluorescence polarization immunoassay (Abbott Tdx): comparison with high-performance liquid chromatography, substrate-labelled fluorescent immunoassay and radioimmunoassay.
An immunoassay based on fluorescence polarization detection (FPIA) has been recently adapted for dibekacin. This has been compared with a reference method (high-performance liquid chromatography), and two other methods used in clinical laboratories for monitoring this aminoglycoside, namely substrate-labelled fluorescent immunoassay (SLFIA) and radioimmunoassay (RIA). FPIA was fast and more reliable than SLFIA or RIA, and offered therefore superior performance. However, its nominal cost per assay is high.
PubMed: 16867630
DOI: 10.1016/0731-7085(86)80023-1