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N Tomono

Publications and source records attributed to N Tomono.

32 records · Page 2Linked to original sources

[Pharmacokinetics of arbekacin in dogs. II. The distribution of arbekacin in tissues].

A new aminoglycoside antibiotic, arbekacin (HBK) was intramuscularly and intravenously administered to Beagle dogs at a dose of 10 mg/kg to study its distribution into various tissues. The results obtained are summarized as follows. Biological half-lives of HBK in serum after intramuscular and intravenous injection were 1.15 hours and 1.00 hour after administration, respectively. These half-lives were similar to the results obtained in previous studies. Maximum concentrations of HBK in tissues and biological fluids after intramuscular injection were the highest in kidney followed by vagina, serum, urinary bladder, uterus, ovarium, lung, parotid gland, trachea, tonsil, gall bladder, pericardiac fluid, thymus, muscle, heart, liver, mandibular gland, bile, aqueous humor, pancreas, cerebrospinal fluid and brain, in this order. Maximum concentrations were found at 4 hours in trachea, aqueous humor and cerebrospinal fluid, and at 2 hours in pericardiac fluid. In other tissues and biological fluids, they were obtained at 0.5-1 hour. Maximum concentrations in tissues and biological fluids after 1 hour intravenous injection were the highest in kidney followed by serum, ovarium, vagina, lung, parotid gland, urinary bladder, uterus, spleen, thymus, pericardiac fluid, gall bladder, trachea, tonsil, heart, liver, pancreas, muscle, mandibular gland, bile, aqueous humor, cerebrospinal fluid and brain in this order. Maximum concentrations were found at 4 hours in trachea, cerebrospinal fluid and bile, and at 2 hours in pericardiac fluid. In other tissues and biological fluids, they were obtained at the end of the infusion. Maximum concentrations in these biological fluids after both intramuscular and intravenous injection were similar to serum concentrations except kidney, trachea, and other biological fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides↗

Recurrent chromosome abnormalities in adult T-cell lymphomas of peripheral T-cell origin.

Cytogenetic studies were performed on 11 Japanese patients with adult T-cell lymphoma of peripheral T-cell origin. All patients had a histologic diagnosis of diffuse lymphoma, and were treated with intensive combination chemotherapy; their median survival was 6 months. Lymphomas were categorized on the basis of the classification proposed by the Lymphoma Study Group of Japan: 5 patients had the features of pleomorphic lymphoma; 3, mixed lymphoma; 2, large-cell lymphoma; and 1, medium-sized-cell lymphoma. The modal chromosome number of abnormal cells was near-diploid in 7, and hypotetraploid in 4 including 3 patients with pleomorphic lymphoma. Abnormalities of the clonal chromosomes were observed in all 11 patients. A translocation of the short arm of 19 at band 19p13 was found in 2 patients with pleomorphic lymphoma and in one patient each with mixed lymphoma and medium-sized-cell lymphoma. A translocation of the short arm of 14, with a break at band 14p12, occurred in 4 patients with pleomorphic lymphoma. In one patient each with mixed lymphoma and large-cell lymphoma, an extra chromosome 3 was found. The numerical change was unique because their lymphomas were further categorized as "angioimmunoblastic lymphadenopathy with dysproteinemia" and "large-cell immunoblastic lymphoma", respectively. Our findings suggest that characteristic chromosome abnormalities occur in adult T-cell lymphoma, and dividing cells in the tetraploid range tend to be predominant in pleomorphic lymphoma.

Adult↗

Acute toxicity and pharmacokinetics of dibekacin mice.

The LD50 values of dibekacin to mice were determined following three different methods of administration, namely, intravenous constant infusion, intravenous bolus injection, and intramuscular injection. The serum levels of dibekacin were pharmacokinetically analyzed. The differences in LD50 values between the methods of administration were discussed from the viewpoints of pharmacokinetics. 1) The LD50 value following the intravenous constant infusion was higher than that following the intravenous bolus injection and approached the level of that following the intramuscular injection, when the infusion rate of the drug was decreased by increasing the infusion period. 2) The biological half-life of dibekacin in mice was 24--45 min. 3) The volume of distribution increased as its dose increased, and a linear correlation was noted between log Vd and log (dose). 4) The difference among the maximum serum concentrations calculated with dibekacin following the administration of LD50 was small, which coincided with the results of the experiment that the serum concentrations of dibekacin at the death following the administration of LD100 were almost the same regardless of the method of administration.

Animals↗

Pharmacokinetics of dibekacin in rabbits and dogs.

The behaviors of dibekacin after three administration methods to rabbits and dogs were pharmacokinetically analysed. 1) In both rabbits and dogs, the pharmacokinetic constants for the intravenous constant infusion and intramuscular injection were similar to each other, and the serum levels after the intravenous constant infusion for 1 hr were similar to those after the intramuscular injection except the peak time. 2) In both rabbits and dogs, Vd increased with the dose and a linear correlation was noted between log Vd and log (dose). 3) The tissue concentrations of dibekacin decreased with the decrease in the serum concentration. 4) A correlation equation, log T 1/2 = 0.194 . log B + 1.128, was obtained, where T 1/2 and B represent the biological half-life of dibekacin and the body weight of animals, respectively. It was suggested that the pharmacokinetic behaviors of dibekacin in human beings can be predicted from the results of the animal experiments.

Animals↗

[Studies of dibekacin eye-drops. Intraocular penetration (author's transl)].

Ocular tissue levels of dibekacin (DKB) were studied in rabbits after instillation of 0.3% DKB eye-drops five times every 5 minutes. (1) In normal eyes, DKB levels were determined in all of the outer parts of eye and some of inner parts such as aqueous humor and vitreous body. Such levels were relatively higher than those of gentamicin. (2) In cauterized eyes by NaOH tissue levels were several times higher than those obtained in normal eyes. (3) Considering these results and MIC levels against both Gram-positive and Gram-negative bacteria such as Pseudomonas aeruginosa or Staphylococcus aureus, it is suggested that 0.3% DKB eye-drops will show effectiveness in clinical use.

Animals↗

[Experimental studies on absorption, distribution and excretion of fosfomycin. I. Absorption distribution and excretion of fosfomycin calcium salt (author's transl)].

In order to develop some oral drug preparations containing calcium salt of fosfomycin ((minus)-cis-1,2-epoxypropylphosphonic acid) which is a new antibiotic, the absorption, distribution and excretion were studied when it was administered orally to fasted test animals such as rats, rabbits and dogs. The results are as follows: 1) In the case of rats, the more dose size was increased, the more ratio of excretion in urine as index of gastrointestinal absorption was reduced and ratio of excretion in stools was adversely increased, which suggested a decrease in absorption efficiency. But, as absolute amount of excretion in urine became larger with dose size, it was considered that increase in dose size would serve for elevation of serum levels. 2) When the calcium salt was given to rats and rabbits in form of solution and suspension, the former was more eminent than the latter regarding to absorption efficiency, as generally known. The solution, however, needed relatively large quantity of water to solubilize the calcium salt, and it was not considered that the absorption efficiency depends on only dissolution step or dissolution rate. 3) Difference of the particle size varying from 1.50 mu(bulk particle size) and 0.64 mu(mechanical limit size) measured by Kozeny-Carman method did not affect on the absorption in rats and dogs. So it was considered that the bulk could be use directly without micronizing in manufacturing process for the oral preparations. 4) There were some differences of absorption among the animal species. Good absorption was shown in turn in rats, dogs and rabbits. These differences might depend not only on physiological factors but also anatomical differences such as length of gastrointestinal tract. 5) In rabbits high concentration was observed successively in kidney, lung, heart and so on. In any organ its level decreased similarly to the serum level, not sustaining its initial high concentration. The calcium salt did not possess any affinity to certain organs. 6) In conclusion, though some differences of gastrointestinal absorption were observed among the animal species, fosfomycin calcium salt was well absorbed without problem of micronizing the bulk particles. Moreover, it was perceived that fosfomycin calcium salt, once distributed, would not remain in particular organs, being excreted out of body.

Administration, Oral↗