[in Japanese]

View full abstract

Seventy Hartley strain guinea pigs (350g body weight at start of the experiment) were used. BB-K8, gentamicin(GM) and kanamycin (KM) were given to the animals intramuscularly for 28 days at following various doses:
BB-K8 40mg/kg 10 guinea pigs GM 100mg/kg 10 guinea pigs BB-K8 100mg/kg 10 guinea pigs KM 100mg/kg 10 guinea pigs BB-K8 200mg/kg 10 guinea pigs KM 200mg/kg 10 guinea pigs GM 40mg/kg 5 guinea pigs KM 400mg/kg 5 guinea pigs
These guinea pigs underwent a differential frequency pinna reflex test in wide frequency range from 20KHz to 0.5KHz before the administration, during the injection and after the last one. For histopathological examination of the inner ears the guinea pigs were subjected to intravital fixation with Wittmaack's fixative under nembutal general anesthesia. Blocks including the bilateral temporal bones were removed from the skulls and then fixed in the same fixativefor 1-2 weeks. After routine procedure for decalcification, dehyration and celloidin embedding, horizontal serial sections of the inner ears were made and stained with hematoxylin-eosin.
The differential frequency pinna reflex test in the 70 guinea pigs indicated positive pinna reflex in 90% at 20KHz and in 100% at 15, 12, 10, 8, 6, 4, 3, 2, 1 and 0.5KHz before start of the administration. Administration of the antibiotics for 28 days occasionally resulted in the pinna reflex loss which always involved the highest frequency, 20KHz and then was followed in relatively regular succession by 15, 12, 10, 8, 6, 4, 3, 2, 1 and 0.5KHz (Tables 1-8). On the other hand, histopathological examination of the inner ears disclosed that the loss of the outer hair cells in the spiral organ which are the most sensitive to the ototoxic antibiotics, occurred always at the basal end of the spiral organ and then spread from there to upper portion of the spiral organ (Tables 9-16).
Based on the differential frequency pinna reflex test in the wide frequency range and extensive histopathological examination of the inner ears, ototoxicity of BB-K8 is considered to be more mild than GM. However, there was not so remarkable difference in ototoxicity between BB-K8 and KM in the present experiment. The result of examination of the guinea pigs received BB-K8 at 40mg/kg and 100mg/kg respectively for 28 days suggests that BB-K8 at expecting clinical dose, 500mg per day (for 28 days) may be safe from ototoxicosis in the inner ears. In the vestibular organs of the animals received BB-K8 there was no decrease in number of the hair cells.

View full abstract

[in Japanese]

View full abstract

In order to develop some oral drug preparations containing calcium salt of fosfomycin ((-)-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 rusults 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 μ(bulk particle size) and 0.64μ(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 succesively 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.

View full abstract

To establish the best usage and dosage of fosfomycin granule and capsules which had been prepared based on our fundamental experiences as described in the first report, absorption of calcium salt contained in both preparations was evaluated using dogs as test animals.
1) Granule containing the calcium salt equivalent to 200 mg of fosfomycin free acid per gshowed almost the same absorption as the bulk (fosfomycin calcium), having no disadvantage due to processing.
(2) Capsules containing the calcium salt equivalent to 250 mg and 500 mg of the free acid per capsule showed slightly more retarded absorption than the bulk, probably due to some inevitable factors such as disintegration rate of capsules and dispersion rate of the calcium salt. But, once dispersed, the calcium salt in capsules was well absorbed as well as the bulk material.
3) Gastrointestinal absorption of granule and the capsule contents was almost the same.
4) Simultaneous administration of capsules and water improved the absorption effic(iency.Thevoelusg hw aedrem inraisthtreart ionw elal ftseur stfaeinededin gw citahu sae d slsiogmhte wdhraotp rebtuatr desdu ffiacbiseonrcpyt ioonf oafb sthoerp tdiorung, tshueg gseesrtuinmgl better clinical advantages than in the fasted animals.
5) Fosfomycin calcium salt in both preparations was well absorbed in the test animals through gastrointestinal tract as well as the bulk calcium salt, without any possible disadvantage caused by processing. In addition, the absorption efficiency was improved by giving with water or meal to the animals.

View full abstract

We have examined the antibacterial activity of the new antibiotic, fosfomycin (FOM) in vitro and in vivo. The following results were obtained.
1. FOM showed a broad antibacterial spectrum.
2. The antibacterial activity of FOM was enhanced in the medium at pH 6 and pH 7, and was also influenced by the addition of rabbit serum, calf serum, glucose-6-phosphate or defibrilated sheep blood to the growth medium, and by the size of inoculum.
3. FOM showed especially strong bactericidal action upon the bacteria at the logarithmic phase.
4. FOM showed remarkable therapeutic effect against most strains of gram-positive and gramnegative bacteria tested in experimental infections of mice.
5. The therapeutic effect of FOM was especially remarkable for infection with Salmonella.
6. The therapeutic effect of FOM was more potent than the other drugs tested against infection of Pseudomonas aeruginosa.
7. It seems that FOM is more active in vivo than in vitro with respect to antibacterial activity.

View full abstract

(1) Ampicillin-cloxacillin for intravenous injection (Rectocillin ‘Kyowa’) was administered to 9 patients 1g or 2g daily for protection of postoperative infections, and good result was obtained in all cases. Eight out of 9 cases were with renal insufficiency. No side effect was encountered.
(2) Rectocillin was administered to 14 patients with infections. The treatment was remarkably effective in 4 cases, and effective in 6 cases. In the cases with renal insufficiency, a daily dose of 1g was effective. The dose administered to the patients with normal renal function was 2g or 4g daily. Neither clinical nor laboratory findings showed evidence of side effect.

View full abstract

Ampicillin-cloxacillin (Rectocillin‘Kyowa’) was administered either orally (capsules) or by intravenous drip infusion to a total of 40 patients and the following results were obtained:
1. Effectiveness obtained in the group received Rectocillin capsules (1,500mg/day) was 80%.
2. Effectiveness obtained in the group received Rectocillin intravenous drip infusion (3-10g/day) was 64.7%.
3. Side effects were encountered in 2 of 40 patients, but none of them were serious, and clinical abnormalities due to this antibiotic were not observed.

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

Clinical effect of amoxicillin was evaluated in 29 cases of the acute infections of ear, nose and throat: 8 cases of acute purulent otitis media, one case of acute otitis externa, one case of furuncle of the ear, 2 cases of acute sinusitis, 12 cases of acute lacunar tonsillitis, 2 cases of pharyngolaryngitis, one case of acute cervical lymphadenitis, one case of phlegmon of the face and one case of acute gingivitis. The following results were obtained from the clinical and laboratory studies.
1) The therapeutic results were excellent in 18 cases, good in 5 cases, fair in 3 cases and poor in 3 cases. The effect was observed in 79.3% of the patients treated.
2) The causative bacteria were: 3 strains of β-Streptococcus hemolyticus, 4 strains of Hemophilus, 4 strains of Staphylococcus aureus, one strain of Diplococcus pneumoniae, one strain of Gram-positive Diplococcus and Gram-negative Bacillus. Clinically good results were obtained in patients infected with β-Streptococcus hemolyticus, Hemophilus and Diplococcus pneumoniae.
3) No side effect was observed with amoxicillin, except slight diarrhea in one case. This side effect disappeared by cessation of the administration.
4) No unfavourable influence was noticed on peripheral blood, liver function nor renal function by administration of amoxicillin.
5) From the results of this series, amoxicillin seems to be useful in the treatment of acute infections of the ear, nose and throat.

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract

[in Japanese]

View full abstract