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The Journal of Antimicrobial... Jun 1987The pharmacokinetics of dibekacin were studied in the rabbit with a dosage regimen of 2 mg/kg at intervals of 12 h. The drug was administered by iv bolus injection, iv...
The pharmacokinetics of dibekacin were studied in the rabbit with a dosage regimen of 2 mg/kg at intervals of 12 h. The drug was administered by iv bolus injection, iv infusion and im injection. Twenty-four hours after the fifth dose, dibekacin concentrations in the renal cortex and medulla, liver, lung and heart were determined. The plasma concentrations showed significant differences between the first and fifth dose when the antibiotic was administered by iv bolus injection. The tissue concentrations also varied significantly according to the route of administration with higher tissue concentrations occurring after iv bolus injection. Tissue binding also varied according to the route of administration and was greatest for the renal cortex and medulla, followed by the lung, liver and heart.
Topics: Animals; Dibekacin; Kanamycin; Kinetics; Male; Rabbits; Tissue Distribution
PubMed: 3610907
DOI: 10.1093/jac/19.6.799 -
Experientia Jul 1980
Topics: Animals; Calcium; Dibekacin; Dose-Response Relationship, Drug; Edetic Acid; Gentamicins; Kanamycin; Neuromuscular Junction; Rats
PubMed: 6772469
DOI: 10.1007/BF01978619 -
Antimicrobial Agents and Chemotherapy Aug 2019ME1100, an inhalation solution of arbekacin, an aminoglycoside, is being developed for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia....
ME1100, an inhalation solution of arbekacin, an aminoglycoside, is being developed for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia. The objective of these analyses was to develop a population pharmacokinetic model to describe the arbekacin concentration-time profile in plasma and epithelial lining fluid (ELF) following ME1100 administration. Data were obtained from a postmarketing study for an intravenous (i.v.) formulation of arbekacin, a phase 1 study of ME1100 in healthy volunteers, and a phase 1b study of ME1100 in mechanically ventilated subjects with bacterial pneumonia. Data from the postmarketing study were utilized to develop a population pharmacokinetic model following i.v. administration, and this model was subsequently utilized as the foundation for development of the model characterizing arbekacin disposition following inhalation of ME1100. The final model utilized two compartments for both plasma and ELF disposition, with movement of arbekacin between the ELF and plasma parameterized using linear first-order rate constants. A bioavailability term was included for the inhalational route of administration, which was estimated to be 19.5% for a typical subject. The model included normalized creatinine clearance (CLcrn) and weight as covariates on arbekacin clearance: CL = (weight/52.2)·[(CLcrn-77)·0.0289 + 2.32]. The model simultaneously described arbekacin concentrations following both i.v. and inhaled administration and provided acceptable fits to the plasma and ELF data ( of 0.922 and 0.557 for observed versus fitted concentrations, respectively). The developed model will be useful for conducting future analyses to support ME1100 dose selection.
Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Dibekacin; Female; Humans; Male; Middle Aged; Models, Biological; Nebulizers and Vaporizers; Pharmaceutical Solutions; Young Adult
PubMed: 31182524
DOI: 10.1128/AAC.00267-19 -
The Japanese Journal of Antibiotics Dec 1982The serum concentration of dibekacin (DKB) were determined in 4 healthy adult volunteers after intramuscular injection, intravenous injection and 1-hour or 2-hour...
The serum concentration of dibekacin (DKB) were determined in 4 healthy adult volunteers after intramuscular injection, intravenous injection and 1-hour or 2-hour intravenous drip infusion of 100 mg of DKB, and 1-hour drip infusion of 50 mg. The mean peak concentration after the 2-hour drip infusion of 100 mg of DKB was a rather low level. While the 1-hour drip infusion of 50 mg of DKB produced a peak concentration of 7.9 micrograms/ml, which is comparable to that after intramuscular injection of 100 mg. In the cases of the 1-hour drip infusion of 100 mg, the peak serum level reached 13.3 micrograms/ml, which is a relatively higher level than that after intramuscular injection of the same dose. Based on the above findings, it is suggested that the 1-hour intravenous drip infusion of DKB in doses of 50 mg to 100 mg be practically applied for therapeutic use.
Topics: Adult; Animals; Anti-Bacterial Agents; Dibekacin; Humans; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Kanamycin; Klebsiella Infections; Lung; Male; Mice; Pneumonia
PubMed: 7182532
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Oct 1985A rapid, simple, and accurate method for the determination of kanamycin and dibekacin in serum by use of high-pressure liquid chromatography is described. The serum...
A rapid, simple, and accurate method for the determination of kanamycin and dibekacin in serum by use of high-pressure liquid chromatography is described. The serum proteins were precipitated with 3.5% perchloric acid containing sodium octanesulfonate. After centrifugation, a sample of the supernatant was directly injected into the chromatograph. The determination of kanamycin and dibekacin was performed by a combination of reverse-phase, ion-pair chromatography, postcolumn derivatization with o-phthalaldehyde, and fluorescence detection. The correlation coefficients with fluorescence polarization immunoassay were 0.996 for kanamycin and 0.957 for dibekacin.
Topics: Chromatography, High Pressure Liquid; Dibekacin; Humans; Kanamycin; Spectrometry, Fluorescence
PubMed: 4073874
DOI: 10.1128/AAC.28.4.521 -
The Journal of Antimicrobial... Jul 1980
Topics: Anti-Bacterial Agents; Azaserine; Dibekacin; Drug Synergism; Escherichia coli; Kanamycin; Staphylococcus aureus
PubMed: 7000744
DOI: 10.1093/jac/6.4.564 -
Die Pharmazie Jun 2019Four potential process related impurities were detected during the impurity profiling study of a semi-synthetic aminoglycoside antibiotic, arbekacin. The current...
Four potential process related impurities were detected during the impurity profiling study of a semi-synthetic aminoglycoside antibiotic, arbekacin. The current preparation process from 3',4'-didehydro-dibekacin easily generates the specific impurities with similar structures to arbekacin that makes hard to separate and identify the residues. HPLC-ELSD and column chromatography loading weakly acidic cation exchange resin were used for the detection and isolation of these process impurities. Based on the synthesis and spectral data (ESI-MS/MS, H NMR, C NMR and 2D-NMR), the structures of these impurities were characterized as dibekacin, 3-N-γ-aminohydroxybutyric (AHB)-dibekacin, 3''-N-AHB-dibekacin and 1,3-N,N-di-AHB-dibekacin. The characterization of these impurities is discussed in detail and our current efforts may help to develop a general strategy for isolation and identification of aminoglycoside products.
Topics: Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Dibekacin; Drug Contamination
PubMed: 31138373
DOI: 10.1691/ph.2019.8242 -
La Nouvelle Presse Medicale Nov 1982The advent of strains resistant to antibiotics in some patients has led to reorientation of research in this field. Demonstration of the mechanism involved in resistance...
The advent of strains resistant to antibiotics in some patients has led to reorientation of research in this field. Demonstration of the mechanism involved in resistance to aminosides has resulted in the development of derivatives active against these resistant strains. Dibekacin, a new aminoside, is the first semisynthetic antibiotic of this class to be developed, and represents the first application of carbohydrate chemistry to the industry. It possesses potent activity and very weak ototoxicity.
Topics: Dibekacin; Drug Resistance, Microbial; Humans; Kanamycin
PubMed: 7155844
DOI: No ID Found -
La Nouvelle Presse Medicale Nov 1982The pharmacokinetics of dibekacin were studied in 23 patients with varying degrees of renal insufficiency. Creatinine clearance was between 4 and 51 ml/min. Chronic...
The pharmacokinetics of dibekacin were studied in 23 patients with varying degrees of renal insufficiency. Creatinine clearance was between 4 and 51 ml/min. Chronic renal insufficiency did not affect maximum serum concentrations, nor the time required to reach a peak level after an intramuscular injection of 1 mg/kg of dibekacin. The maximum concentration was 4 to 5 mcg/ml and the peak obtained within the first hour. Renal insufficiency caused a very marked prolongation in the serum half-life of elimination. This rose from 6 hours in moderate renal insufficiency to 50 hours in a patient with a clearance of a few millilitres. Whatever the degree of renal insufficiency, it should be noted that urinary concentrations remained markedly higher than the MIC of organisms sensitive to the aminoglycoside. Dibekacin is highly dialysable, being virtually totally extracted during a 6 hours dialysis session using a membrane of 1 m2 surface area. An outline of dose adaptations in relation to the degree of renal insufficiency is suggested on the basis of these pharmacokinetic data.
Topics: Adult; Aged; Dibekacin; Female; Humans; Kanamycin; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis
PubMed: 7155849
DOI: No ID Found -
Paediatrica Indonesiana 1982
Clinical Trial
Topics: Child; Child, Preschool; Clinical Trials as Topic; Dibekacin; Female; Humans; Infant; Kanamycin; Male; Urinary Tract Infections
PubMed: 6763182
DOI: No ID Found