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European Journal of Clinical... Oct 1980The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance < 5 ml/min) undergoing haemodialysis sessions lasting...
The pharmacokinetics of Dibekacin were studied in 10 patients with terminal renal impairment (creatinine clearance < 5 ml/min) undergoing haemodialysis sessions lasting 4 h. The dialyzers were either the Gambro Lundia Major 13.5 or the Ultra Flo II 1.4., and the patients were divided into two groups according to the dialyzer used. Blood flow varied between 250 and 280 ml/min and dialyzate flow between 450 and 600 ml/min. All patients received a single i. v. dose of Dibekacin 1.5 mg/kg at the beginning of the dialysis session. The concentration of the antibiotic at the input and the output of the dialyzer were determine microbiologically by a plate diffusion method using B. subtilis as the test organism. The intravenously administered antibiotic followed an open two-compartment kinetic model. The type of dialyzer used did not influence the dialysis of Dibekacin. Haemodialysis significantly increased the elimination rate of the antibiotic with respect to the interdialysis periods. The plasma half-life in the slow disposition phase fell from 30 h in the interdialysis period to 4.0 h during dialysis sessions. From the calculated pharmacokinetic parameters, a dosage regimen for this kind of patient is proposed.
Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Dibekacin; Humans; Kanamycin; Kinetics; Middle Aged; Renal Dialysis
PubMed: 7439256
DOI: 10.1007/BF00561393 -
The Journal of Pharmacology and... Nov 1983Like many amphiphilic cationic drugs, aminoglycosides are able to produce phospholipidosis, mainly by inhibiting enzymes involved in phospholipid metabolism....
Like many amphiphilic cationic drugs, aminoglycosides are able to produce phospholipidosis, mainly by inhibiting enzymes involved in phospholipid metabolism. Phosphoinositides have been suggested to function as receptors for aminoglycosides. Therefore, we investigated the influence of these drugs upon phosphoinositide metabolism by measuring the 32P-incorporation into the polyphosphoinositides, using the rat erythrocyte membrane as a model. Depending upon the experimental conditions, neomycin induced a decrease and/or an increase in the 32P-labeling of triphosphoinositides (TPI) and of diphosphoinositides (DPI), respectively. These variations were rapid and depended upon the drug concentration. At 0.3 mM, neomycin reversed the distribution of radioactivities associated with DPI and TPI without modifying the total radioactivity incorporated. This drug concentration altered neither the Mg++-activated TPI-specific phosphomonoesterase activity nor the Ca++-activated polyphosphoinositide phosphodiesterase activity. It appears likely that the drug inhibits the DPI-kinase activity, by interacting with DPI and thereby lowering the substrate availability. Over the range of concentrations studied (up to 1-2 mM), gentamicin, kanamycin and dibekacin behave as neomycin. However, their effects could be observed only at drug concentrations higher than those of neomycin. By contrast, streptomycin and amikacin did not alter the 32P-labeling of TPI and of DPI. The order of potency of aminoglycosides for the impairment of the phosphoinositide interconversion was neomycin, gentamicin, dibekacin, kanamycin. A possible relationship between the toxicity of aminoglycosides and their capacity to impair the phosphoinositide metabolism is discussed.
Topics: Amikacin; Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Erythrocyte Membrane; Gentamicins; Kanamycin; Neomycin; Phosphatidylinositols; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Streptomycin
PubMed: 6313902
DOI: No ID Found -
Therapeutic Drug Monitoring Feb 2020Arbekacin (ABK) is used to treat infections caused by methicillin-resistant Staphylococcus aureus and is used widely for the treatment of febrile neutropenia (FN). As...
BACKGROUND
Arbekacin (ABK) is used to treat infections caused by methicillin-resistant Staphylococcus aureus and is used widely for the treatment of febrile neutropenia (FN). As ABK has a narrow therapeutic concentration window, the dosage must be adjusted via therapeutic drug monitoring. However, the influence of the physiology of patients with FN on the pharmacokinetic (PK) parameters of ABK remains unclear. Therefore, we examined this influence on ABK PK parameters.
METHOD
We performed a retrospective cohort study using data from patients with a hematologic malignancy who were ≥18 years and had been administered ABK. We excluded patients who did not receive therapeutic drug monitoring and had an estimated glomerular filtration rate (eGFR) of <30 mL/min, because clinically sufficient data would not be available.
RESULT
Of the 99 enrolled patients, 25 did not have FN and 74 had FN. Arbekacin clearance (CLabk) was shown to correlate with eGFR in patients with FN (r = 0.32, P = 0.0062) and without FN (r = 0.50, P = 0.01). CLabk was higher in patients with FN than in those without FN. In addition, in the eGFR of <100 mL/min group (normal renal function), CLabk and CLabk/eGFR were also higher in patients with FN than in those without FN.
CONCLUSIONS
CLabk was increased in patients with FN and normal renal function; therefore, we propose an increased ABK dose for patients with FN and normal renal function.
Topics: Adult; Aged; Anti-Infective Agents; Cohort Studies; Dibekacin; Drug Monitoring; Febrile Neutropenia; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Retrospective Studies
PubMed: 31323015
DOI: 10.1097/FTD.0000000000000678 -
Carbohydrate Research Mar 1997Three 2"-modified dibekacin-analogs have been prepared as potential compounds active against resistant bacteria producing 2"-O-phosphotransferases; one is...
Synthesis of 2"-oxidized derivatives of 5-deoxy-5-epi-5-fluoro-dibekacin and -arbekacin, and study on structure-chemical shift relationships of urethane(or amide)-type NH protons in synthetic intermediates.
Three 2"-modified dibekacin-analogs have been prepared as potential compounds active against resistant bacteria producing 2"-O-phosphotransferases; one is 5-deoxy-5,2"-diepi-5-fluorodibekacin (9) prepared from a suitably protected 2"-O-triflyl derivative through the 2" 3"-cyclic carbamate, and the others are 2"-oxo derivatives (12 and 22, both as the hydrate) of 5-deoxy-5-epi-5-fluoro-dibekacin and -arbekacin prepared through oxidation at C-2" of suitably protected derivatives. Relationships between the t-butoxycarbonyl(= Boc)-NH-shifts of per-N-Boc synthetic intermediates and their structures were studied. It was found that the shifts, measured in pyridine-d5 at 80 degrees C, which spread over a close range (delta 6-7 ppm), are sensitively influenced by nearby and surrounding groups around the BocNH group in respect of electron-withdrawing character, hydrogen bonding (BocNH ... acceptor), and also solvent effects (BocNH ... NC5H5).
Topics: Amides; Anti-Bacterial Agents; Carbohydrate Conformation; Carbohydrate Sequence; Dibekacin; Microbial Sensitivity Tests; Models, Molecular; Molecular Sequence Data; Molecular Structure; Oxidation-Reduction; Protons; Urethane
PubMed: 9098957
DOI: 10.1016/s0008-6215(96)00318-7 -
International Journal of Clinical... Jan 1987Dibekacin pharmacokinetics was studied in ten healthy volunteers and six patients with renal failure presenting Clcr less than 10 ml X min-1 per 1.73 m2 of body surface,...
Dibekacin pharmacokinetics was studied in ten healthy volunteers and six patients with renal failure presenting Clcr less than 10 ml X min-1 per 1.73 m2 of body surface, given as a slow intravenous bolus to the volunteers and as a 30-minute intravenous infusion to the patients. The antibiotic was assayed in plasma and urine by means of a microbiological method using Bacillus subtilis. A two-compartment kinetic model was used to describe the bi-phasic decline of the plasma concentration thus establishing the different pharmacokinetic parameters. Elimination parameters beta, k10 and total body clearance were markedly diminished in renal patients (p less than 0.001): t1/2 beta was 2.0 h, k10 = 0.016 min-1 and Cl = 0.87 ml X min-1 kg body weight in normal subjects and t1/2 beta = 21.4 h, k10 = 0.0011 min-1 and Cl = 0.131 ml X min-1 per kg in the patients. Other kinetic parameters, as distribution (alpha) and transfer (k12, k21) constants were lower in patients than in volunteers. Also the different terms of volume of distribution of the two-compartment model (V1, Vdss, Vdarea) were significantly higher in patients than in normal subjects (p less than 0.05). A good correlation (r = 0.987) between patients' beta constant and creatinine clearance was found. A similar relationship between serum creatinine levels and disposition half-life was found (r = 0.955). Urinary recovery at 24 h was 89.0% of the dose given to normals and 15.8% of the dose given to patients.
Topics: Adult; Creatinine; Dibekacin; Female; Half-Life; Humans; Kanamycin; Kidney Failure, Chronic; Kidney Function Tests; Kinetics; Male; Metabolic Clearance Rate
PubMed: 3557728
DOI: No ID Found -
Research Communications in Chemical... Sep 1981To evaluate the nephrotoxicity of the new aminoglycoside, dibekacin, relative to gentamicin, we administered both drugs in doses of 40 and 120 mg/kg per day to male and... (Comparative Study)
Comparative Study
To evaluate the nephrotoxicity of the new aminoglycoside, dibekacin, relative to gentamicin, we administered both drugs in doses of 40 and 120 mg/kg per day to male and female Fischer 344 rats. At sacrifice, we determined serum creatinine, in vitro renal cortical uptake of 14C N-methyl nicotinamide and para-aminohippurate, renal cortical antibiotic concentrations, and real histology. Dibekacin and gentamicin were similar in overall toxicity. Dibekacin differed from gentamicin and other aminoglycosides (1) in failing to cause early transient stimulation of para-aminohippurate uptake in male rats and (2) in the location of histologic damage at the 120 mg/kg dose. We conclude that: 1) in this model, dibekacin is comparable to gentamicin in nephrotoxic potential, and 2) the lack of early stimulation of para-aminohippurate uptake in male rates after dibekacin treatment may be related to greater initial injury to the late proximal tubule than is caused by gentamicin.
Topics: Animals; Anti-Bacterial Agents; Dibekacin; Female; Gentamicins; Glomerular Filtration Rate; Kanamycin; Kidney; Male; Rats; Rats, Inbred F344; p-Aminohippuric Acid
PubMed: 7330450
DOI: No ID Found -
Bulletin de La Societe Belge... 1984
Topics: Animals; Anterior Chamber; Dibekacin; Double-Blind Method; Electroretinography; Gentamicins; Kanamycin; Rabbits; Retina; Therapeutic Irrigation
PubMed: 6545511
DOI: No ID Found -
La Nouvelle Presse Medicale Nov 1982Major abdominal surgery often involves severe postoperative infections with various pathogens: enterobacteriaceae, staphylococcus and anaerobic bacteria. For this reason...
Major abdominal surgery often involves severe postoperative infections with various pathogens: enterobacteriaceae, staphylococcus and anaerobic bacteria. For this reason a strong antibiotherapy can be necessary in the case of an infectious disease. Dibekacin was administered at a daily dose of 3 mg/kg to 22 patients suffering from very severe postoperative infection. In all the cases dibekacin was combined with a beta-lactamine and in some with nitro-imidazole derivative. The results were especially favourable in all of these cases and a good tolerance was observed.
Topics: Abdomen; Adult; Aged; Bacterial Infections; Dibekacin; Female; Humans; Kanamycin; Male; Middle Aged; Postoperative Complications
PubMed: 7155855
DOI: No ID Found -
[Dibekacin in the treatment of urinary tract infections in children. Efficacy and pharmacokinetics].Revista Chilena de Pediatria 1982
Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Dibekacin; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Infant; Infant, Newborn; Kanamycin; Kinetics; Male; Urinary Tract Infections
PubMed: 7178560
DOI: No ID Found -
Nihon Naika Gakkai Zasshi. the Journal... Oct 1992
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Combinations; Drug Therapy, Combination; Fosfomycin; Humans; Imipenem; Methicillin Resistance; Staphylococcal Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Vancomycin
PubMed: 1469319
DOI: No ID Found