dibekacin and Body-Weight

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

Immature renal function in neonates requires antibiotic dosage adjustment. Population pharmacokinetic studies were performed to determine the optimal dosage regimens for three types of antibiotics: an aminoglycoside, arbekacin; a glycopeptide, vancomycin; and a carbapenem, panipenem. Eighty-three neonates received arbekacin (n = 41), vancomycin (n = 19), or panipenem (n = 23). The postconceptional ages (PCAs) were 24.1 to 48.4 weeks, and the body weights (BWs) ranged from 458 to 5,200 g. A one-compartment open model with first-order elimination was applied and evaluated with a nonlinear mixed-effect model for population pharmacokinetic analysis. In the fitting process, the fixed effects significantly related to clearance (CL) were PCA, postnatal age, gestational age, BW, and serum creatinine level; and the fixed effect significantly related to the volume of distribution (V) was BW. The final formulas for the population pharmacokinetic parameters are as follows: CL(arbekacin) = 0.0238 x BW/serum creatinine level for PCAs of <33 weeks and CL(arbekacin) = 0.0367 x BW/serum creatinine level for PCAs of > or = 33 weeks, V(arbekacin) = 0.54 liters/kg, CL(vancomycin) = 0.0250 x BW/serum creatinine level for PCAs of <34 weeks and CL(vancomycin) = 0.0323 x BW/serum creatinine level for PCAs of > or = 34 weeks, V(vancomycin) = 0.66 liters/kg, CL(panipenem) = 0.0832 for PCAs of <33 weeks and CL(panipenem) = 0.179 x BW for PCAs of > or = 33 weeks, and V(panipenem) = 0.53 liters/kg. When the CL of each drug was evaluated by the nonlinear mixed-effect model, we found that the mean CL for subjects with PCAs of <33 to 34 weeks was significantly smaller than those with PCAs of > or = 33 to 34 weeks, and CL showed an exponential increase with PCA. Many antibiotics are excreted by glomerular filtration, and maturation of glomerular filtration is the most important factor for estimation of antibiotic clearance. Clinicians should consider PCA, serum creatinine level, BW, and chemical features when determining the initial antibiotic dosing regimen for neonates.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bayes Theorem; Body Weight; Creatinine; Dibekacin; Female; Gestational Age; Glomerular Filtration Rate; Humans; Infant, Newborn; Male; Models, Biological; Population; Thienamycins; Vancomycin

Seven N-alkylsulfonate derivatives of an aminoglycoside antibiotic, dibekacin, were prepared and their nephrotoxicity was examined. Using water-supplied and water-depleted rats and the BUN value as a nephrotoxic measure, dibekacin-di-N-methanesulfonate, pentasodium dibekacin-penta-N-methanesulfonate, -penta-N-ethanesulfonate, disodium dibekacin-di-N-methanesulfonate sesquisulfate, disodium and dipotassium dibekacin-di-N-ethanesulfonate sesquisulfates and sodium dibekacin-mono-N-ethane-sulfonate disulfate showed low nephrotoxicity as compared to that of the original dibekacin sulfate. Notably, dibekacin-di-N-methanesulfonate caused little change in the BUN value and was bioactive in vitro but not active in vivo against a Pseudomonas aeruginosa infection model in mice. Among the bioactive N-alkylsulfonates in vivo, disodium and dipotassium dibekacin-di-N-ethanesulfonate sesquisulfates showed a lower degree of elevation of BUN, urine volume and urine protein, lower mortality and better body weight gain than those of dibekacin sulfate during consecutive treatment for 12 and 28 days.

Topics: Animals; Bacteria; Blood Urea Nitrogen; Body Weight; Chemical Phenomena; Chemistry; Dibekacin; Kanamycin; Kidney Diseases; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Rats; Rats, Inbred Strains; Urodynamics

Intramuscular administration of dibekacin or gentamicin to Fischer rats at doses of 10, 20 and 40 mg/kg for 11 days gave polyuria, enzymuria and cytauria. These changes were suppressed completely or partially by the simultaneous administration of glucarolactam sodium or potassium salt. The ameliorating results were supported by serum and histopathological analyses on day 12. A rise in BUN and serum creatinine levels was partially or completely suppressed and histopathological scores were improved by co-administration of glucarolactam salts.

Topics: Animals; Body Weight; Creatinine; Dibekacin; Gentamicins; Glucaric Acid; Kanamycin; Kidney; Kidney Diseases; Male; Organ Size; Rats; Rats, Inbred F344; Sugar Acids; Urodynamics

In order to comparatively examine damage to vestibular and auditory organs, aminoglycoside antibiotics, panimycin (DKB) and gentamicin (GM), were intramuscularly injected to cynomolgus monkeys in an identical daily dose regimen (25 and 50 mg/kg) for a 35-day period. No damage to these organs was found in the DKB 25 mg/kg group, but slight vacuole formation was found in 33% of the cristae ampullares in the DKB 50 mg/kg group. In the GM 25 mg/kg and GM 50 mg/kg groups, similar vacuole formations, as well as sensory hair cell loss even at the basal end of the cochlea were found. Compared to the DKB groups, the GM groups exhibited greater damage to the vestibular and auditory organs, and even fatal effects. The ototoxicity of GM seemed to be stronger in cynomolgus monkeys than in guinea pigs.

Topics: Acoustic Maculae; Aminoglycosides; Animals; Body Weight; Dibekacin; Female; Gentamicins; Kanamycin; Labyrinth Diseases; Macaca fascicularis; Organ of Corti; Reflex; Saccule and Utricle

Dibekacin sulphate (DKB), a new aminoglycoside antibiotic developed on the theory of bacterial resistance, was given by intravenous injection to groups of female Beagle dogs at dosages of 2.5, 5.0, 10.0 or 25.0 mg/kg/day for 13 weeks. Physiological saline was given as a control. Some dogs given 5.0 or 10.0 mg/kg/day were retained undosed for a further 5 weeks in order to assess recovery. Premature deaths from acute renal tubular nephrosis occurred in dogs given 25.0 and 10.0 mg/kg/day. Dogs which survived treatment at 10.0 mg/kg/day showed marked elevation of circulating urea and creatinine concentrations after 4 weeks' treatment but thereafter the increases became less obvious. Varying degrees of renal cortical tubular dilatation, basophilia, degeneration or necrosis were seen in the kidneys of all dogs examined after 13 weeks treatment although no clinical impairment of renal function was detectable at dosages up to 5.0 mg/kg/day. These changes had essentially regressed in dogs examined 5 weeks after the last dose of DKB at 5.0 mg/kg/day. All the adverse clinical and histological effects noted, following any dose level of DKB tested, could be attributed to renal changes.

Topics: Animals; Blood Chemical Analysis; Body Weight; Dibekacin; Dogs; Drinking; Eating; Female; Injections, Intravenous; Kanamycin; Kidney; Kidney Tubular Necrosis, Acute; Organ Size

The toxic effects of dibekacin sulfate (DKB) in male and female rats were examined in chronic toxicity test (intraperitoneal injection), and the following results were obtained. 1) No death was noted in both male and female. 2) In general conditions, the excretion of soft or diarrheal stool was noted in groups of more than 20 mg/kg of either sex. The mean body weight was less than the control during a certain period in the male group of 40 mg/kg and in the female group of 20 mg/kg. But, in the food intakes, no particular change was noted in each group of either sex. 3) In the auricle reflex, no abnormality was noted in each group of either sex. 4) In the hematological test, the findings such as an increase of BUN, anemia, etc. were noted in the groups more than 10 mg/kg of male and more than 20 mg/kg of female. 5) In the histopathological study, evident degenerative changes of renal tubular epithelia were noted in the groups which were administered more than 20 mg/kg of DKB in both male and female, but no evident pathological findings due to the renal failure were noted in the groups of less than 10 mg/kg. Several slight changes of the thyroid gland noted in a few rats of DKB administration group of both male and female seemed to be artifact, and inflammatory changes owing to intraperitoneal injection were occasionally noted in the peritoneum of DKB injected animals. 6) Considering the above results, "the maximal non effective dose" was estimated to be 10 mg/kg in both male and female.

Topics: Animals; Body Weight; Dibekacin; Eating; Female; Injections, Intraperitoneal; Injections, Intravenous; Kanamycin; Kidney; Liver; Male; Organ Size; Rats; Reflex, Acoustic

Dibekacin sulfate (DKB) dissolved in physiological saline J.P. was administered to rats intraperitoneally and rabbits intravenously for subacute 35-day toxicity test. The results were as follows: I. Wistar-strain rats (1) All the animals of both male and female died in the group with 500 mg/kg. (2) In general conditions stretching physical positions, decrease in spontaneous movements, decrease in respiration rates, unsteady steps of walking and muscular relaxation developed in the groups of high doses of either sex. The effects through the administration of this drug were also noted on the progress of body weights and food intakes in the groups of high doses. (3) In the hematological and histopathological studies, degenerative and reparative changes of tubular epithelia were evidently noted in the groups which were administered more than 100 mg/kg of DKB in both male and female. No pathological findings were noted in administration groups less than 20 mg/kg. (4) Microscopically, slight inflammatory changes were noted in the bladder of the male groups of high doses and the direct stimulative effects on the peritoneum due to intraperitoneal administration were noted but slightly in the serous membrane of the liver, spleen and the gastrointestinal tracts. (5) Judging from the above-mentioned results, "the maximal non toxic dose" through the intraperitoneal administration to rats of this drug was assumed 20 mg/kg in either sex. II. Albino rabbits (1) Neither remarkable change in the general conditions nor death was noted in each administration group. (2) The increase in the mean body weight in each group was almost similar to the control value. They consumed the amounts of food given. (3) The specific abnormal finding was not noted in the hematology and biochemical tests of serum or urine. (4) Since no change was noted on ERG in each rabbits, we estimate there is no effect to the visual organs. (5) In histopathological study, several changes revealed in some organs through the macroscopic findings, organ weights and microscopic findings but they were no more the serious changes attributable to administration. (6) We estimate "the maximal non effective dose" in this test was 10 mg/kg.

Topics: Animals; Body Weight; Dibekacin; Eating; Female; Injections, Intravenous; Kanamycin; Kidney; Liver; Male; Organ Size; Rabbits; Rats; Reflex, Acoustic

Topics: Animals; Anti-Bacterial Agents; Body Weight; Dibekacin; Disease Models, Animal; Ear, Inner; Gentamicins; Hypertension; Injections, Intramuscular; Kanamycin; Male; Rats; Ribostamycin; Tissue Distribution

Topics: Acoustic Stimulation; Animals; Body Weight; Dibekacin; Ear, Inner; Embryo, Mammalian; Female; Gentamicins; Guinea Pigs; Hearing; Injections, Intramuscular; Kanamycin; Male; Maternal-Fetal Exchange; Methods; Pregnancy