Disease relevance of HAPA-gentamycin B

• The results of the present study show that the renal toxicity of isepamicin was maximal at 1400 h (midlight period) and minimal at 0200 h (middark period) [1].
• Six patients received 15 mg of isepamicin per kg of body weight [2].
• Postanitbiotic and sub-MIC effects of azithromycin and isepamicin against Staphylococcus aureus and Escherichia coli [3].
• Activity of isepamicin and selection of permeability mutants to beta-lactams during aminoglycoside therapy of experimental endocarditis due to Klebsiella pneumoniae CF104 producing an aminoglycoside acetyltransferase 6' modifying enzyme and a TEM-3 beta-lactamase [4].
• In end-stage renal failure, isepamicin is eliminated by haemodialysis, but the administration interval should be determined by monitoring the plasma concentration [5].

High impact information on HAPA-gentamycin B

• Escherichia coli expressing exogenous aac(6')-Iae showed resistance to amikacin, dibekacin, isepamicin, kanamycin, netilmicin, sisomicin, and tobramycin but not to arbekacin, gentamicins, or streptomycin [6].
• Clinical pharmacokinetics and pharmacodynamics of isepamicin [5].
• With isepamicin, it is proposed to achieve a 1-hour concentration (30 minutes after a 30-minute infusion) >40 mg/L to maximise bactericidal efficacy, and a 'trough' concentration (at the end of the administration interval) <5 mg/L to minimise toxicity [5].
• Isepamicin kinetics are linear in the range 7.5 to 25 mg/kg, so that dosage adjustments, if necessary, are straightforward [5].
• Isepamicin is not bound to plasma proteins, and it distributes in extracellular fluids and into some cells (outer hair cells, kidney cortex) by active transport [5].

Chemical compound and disease context of HAPA-gentamycin B

• Cations did not affect the susceptibilities of other Pseudomonas species, Enterobacteriaceae, Staphylococcus aureus, or Streptococcus faecalis to Sch 21420 or amikacin [7].
• A total of 34 patients with intractable chronic respiratory tract infections were treated with isepamicin and/or piperacillin in different dosage regimens [8].
• In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 15 mg/Kg dose of isepamicin [9].
• New antibiotics for gram-negative bacteria resistant to other agents are carbapenems, aztreonam, quinolones and isepamicin [10].

Biological context of HAPA-gentamycin B

• The pharmacokinetics of isepamicin following administration of a 1-g dose were evaluated for 18 healthy male volunteers between the ages of 26 and 38 [11].
• NMR spectroscopy, combined with molecular modeling, was used to determine the conformations of isepamicin and butirosin A in the active site of aminoglycoside 6'-N-acetyltransferase-Ii [AAC-(6')-Ii] [12].
• The areas under the plasma concentration-time curves at infinity for isepamicin (196 micrograms*h/ml) and total radioactivity (164 micrograms*h/ml) were similar, indicating no biotransformation of isepamicin [13].
• The spectrum of isepamicin is most similar to that of amikacin, another aminoglycoside with high enzyme stability [14].

Anatomical context of HAPA-gentamycin B

• The results give evidence for linear uptake kinetics of isepamicin in the inner ear tissue and may be directly relevant to the clinical dosing of the drug [15].
• The isepamicin concentrations in the cochlear duct tissue (organ of Corti plus lateral wall) and the cochlear nerve tissue were determined separately [15].
• Immunogold labeling studies showed that isepamicin was essentially localized in the lysosomes of proximal tubular cells in all treated groups, but the density of the gold particles over the lysosomes was higher in animals treated at 1400 than at 0200 h [1].
• Column liquid chromatographic determination of isepamicin in nasal cavity using gauze [16].
• Diffusion of isepamicin into cancellous and cortical bone tissue [9].

Associations of HAPA-gentamycin B with other chemical compounds

• The susceptibility data determined in vitro, with MICs (in micrograms per milliliter) of amikacin and isepamicin for LoT and HiT of 4 and 0.5 and 32 and 8, respectively, were, however, not predictive of the in vivo efficacies of the drugs [17].
• In vitro activity of Sch 21420, derivative of gentamicin B, compared to that of amikacin [18].
• Tigecycline, carbapenems, and isepamicin exhibited better or comparable in vitro activities against a wide spectrum of commonly encountered bacteria than other comparator antimicrobials and may represent therapeutic options for infections due to multidrug-resistant pathogens [19].
• In vitro activities of tigecycline, ertapenem, isepamicin, and other antimicrobial agents against clinically isolated organisms in Taiwan [19].
• The isepamicin rabbits receiving mivacurium 0.18 mg/kg or rocuronium 0.6 mg/kg had an accelerated recovery from neuromuscular blockade compared with those receiving placebo [20].

Gene context of HAPA-gentamycin B

• Effects of some antibiotics on activity of glucose-6-phosphate dehydrogenase from human erythrocytes in vitro and effect of isepamicin sulfate on activities of antioxidant enzymes in rat erythrocytes [21].
• The CLP of isepamicin and CLCR were significantly related [(COP = 0.391.[CLCR] + 1.83; r2 = 0.878)] [22].
• The MICs of amikacin and isepamicin, their bactericidal effects, and AAC(6')-Ib production appeared to be well correlated among the clinical isolates and the transconjugants [17].
• Isepamicin (formerly SCH 21420 or 1-N-HAPA-gentamicin B) is a novel broad-spectrum aminoglycoside which possesses a high level of stability to aminoglycoside inactivating enzymes and low levels of toxicity to the kidney and inner ear [14].

Analytical, diagnostic and therapeutic context of HAPA-gentamycin B

• Population pharmacokinetic study of isepamicin with intensive care unit patients [23].
• In a randomized crossover fashion, each volunteer received doses of isepamicin by a 30-min intravenous infusion and as an intramuscular injection [11].
• As expected, the maximum concentration of isepamicin in serum following intramuscular injection (37.2 microg/ml) was lower than the observed concentration at the end of infusion (66.7 microg/ml) [11].
• Levels of isepamicin in plasma and urine were determined by a specific high-performance liquid chromatography method [24].
• Blood samples were collected at specified times after dosing and assayed for isepamicin by a validated radioimmunoassay method [11].

References