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1. Serum, peripheral and thoracic lymph concentrations of tobramycin, dibekacin and amikacin were determined at various time intervals up to 6 hours following intramuscular administration of 4 mg/kg to dogs.
Peak serum concentrations of each antibacterial agents occurred within one hour after administration.
The peak lymphatic concentrations occurred in 1.5-2 hours after administration.
Following peak peripheral lymph concentration,the concentration in peripheral lymph exceeded than that of serum.The concentrations of each antibacterial agent in thoracic lymph were nearly equal to serum concentration.Peak peripheral lymph concentrations were always lower than the peak serum concentrations.
2. Serum and pancreatic fluid concentrations of tobramycin,dibekacin and amikacin were determined at various time intervals up to 6 hours following intramuscular adminisration of 4 mg/kg to dogs.
Peak pancreatic fluid concentrations of each antibacterial agents occurred within 1.5 hours after administration.The concentrations rate of tobramycin to the pancreatic fluid was superior to those of dibekacin and amikacin.

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Cefazolin,a member of the cephalosporins,exhibits a strong antibacterial activity against Grampositive cocci and Gram-negative rods,e.g.E.coli and Klebsiella,and has a pharmacokinetic feature of producing long-sustained,high serum levels. We administered cefazolin to8immature and Gnewborn infants in a single intravenous dose of25mg/kg and investigated the time course of serum levels of the drug thus yielded in relation to the time in days elapsing from birth (the infants being divided into2groups,one aged3days or less and the other aged4days or more). Five younger children were also administered with cefazolin in the same manner as mentioned above and were then determined for serum levels of the drug,which were compared with those observed in newborn infants. The results are summarized as follows:
1) Immature infants aged3days or less gave serum levels of the drug of62-115μg/ml and22.5-65μg/ml, respectively, at 30 minutes and 6 hours after the administration, with the half-life-being estimated at 5.48 hours. In immature infants4days or more of age,on the other hand,serum levels of the drug yielded at1hour and6hours after dosing were144-251μg/ml and 25.1-125μg/ml, respectively, hence with a shorter half-life of2.73hours.
2) Serum levels of the drug yielded in newborn infants aged3days or less were84-170μg/ml at 30 minutes and 45-79.4μg/ml at6hours after administration, with the half-life being found at4.52 hours.The corresponding values for newborns4days or more of age are not stated here because there are only 2 cases available.
3) Younger children gave blood levels of the drug of150-247μg/ml at 30 minutes and7.9-19.0μg/ml at6hours after administration,with a half-life of 1.51 hours.
These results led us to conclude that the intravenous administration of cefazolin at a dosage of 25 mg/kg b. i. d.proves to be reliably effective in the prevention and treatment of infection in immature and newborn infants aged3days or less.

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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 100mg/kg of DKB in both male and female. No pathological findings were noted in administration groups less than 20mg/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 20mg/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 10mg/kg.

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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.

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Fosfomycin calcium (FOM-Ca) was orally administered to Wistar rats for 60 consecutive days in males and 14 consecutive days in females in varying doses of 140 mg/kg, 700 mg/kg and 1,400 mg/kg, and then the animals were subjected to mating.It was further administered to pregnant female rats for another week to investigate its effects upon the embryos and fetus.The following results were obtained.
1) In parent animals,soft stools were noted in both sexes of the groups with higher doses,but otherwise there was no remarkable abnormality noted.
2) No increase was seen in the rates of development of dead embryos or externally abnormal fetus.
3) Skeletal abnormality was seen only slightly in the animals of the group with 700 mg/kg, but otherwise all the other groups were similar to the control group,showing that there would be no adverse effects by the tested drug upon the fetal skeletal structure.
4) On the ground of the above-mentioned test results,it was claimed that FOM-Ca exerts adverse effects upon the fetus of rats even in the dose of 700 mg/kg and that the safe dose to fetus of rats would be 140 mg/kg.It was also judged that it has no teratogenicity through administration before or at the initial stage of gestation.

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As previously reported 1, 2), a new antitumor anthracycline antibiotic aclacinomycin A (ACM) was isolated from Streptomyces galilaeus MA144-M1 (ATCC 31133). It was characterized and the structure was determined. In this paper, the physicochemical properties and stability of ACM hydrochloride (ACM-HCl) are described.

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1) A focal infection was prepared by inoculation of staphylococci into rat gingiva. Then, concentrations in oral tissues (gingiva,tongue and masseter), serum and liver of the infected rats which were given ciclacillin,ampicillin,cephalexin and minocycline in a dose of 100 mg/kg p. o. were investigated and effects of serratiopeptidase (20 mg/kg) onthese concentrations were studied.
2) Concentrations of ciclacillin in the oral tissues were approximately 10% of a serum level. A gingival concentration was elevated 8.5-fold by pretreatment with serratiopeptidase.A concentration in infected gingiva was 2.5-fold of that of another side of gingiva.
3) Concentrations of ampicillin in the oral tissues were approximately 15% of a serum level. A gingival concentration was elevated 5.7-fold by pretreatment with serratiopeptidase.A concentration in infected gingiva was 2.2-fold of that of another side of gingiva.
4) Concentrations of cephalexin in the oral tissues were approximately 3 to 5-fold of a serum level except that in masseter.A gingival concentration was slightly elevated (1.1-fold) by pretreatment with serratiopeptidase.A concentration in infected gingiva was 1.7-fold of that of another side of gingiva.
5) Concentrations of minocycline in the oral tissues were 1.3 to 7.2-fold of a serum level. A gingival concentration was elevated 2.2-fold by pretreatment with serratiopeptidase.A concentration in infected gingiva was 3.1-fold of that of another side of gingiva.
6) Gingival concentrations of antibiotics were higher than those of tongue and masseter and serratiopeptidase elevated gingival concentrations.

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The most effective administration method of polymyxin B (PL-B), a peptide antibiotic,has been studied in the experimental mice infection with Pseudomonas aeruginosa.
1) Pseudomonas aeruginosa damaged by PL-B, when the drug was free,immediately began to regrow in vitro.
2) The therapeutic efficacy of PL-B on multiple administration was less effective than its single administration.
3) An important factor to decide the therapeutic efficacy of PL-B was the high drug concentration in plasma and peritoneal fluid.

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[in Japanese]

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