Critical cardiac contamination may occur during extracorporeal circulation in open heart surgery. Prophylactic administration of cephalothin sodium (CET) was studied for their safe and adequate serum concentration after open heart surgery in infants and adults. Methods of administration of CET were discussed for infants and adults.

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Dibekacin (3', 4'-dideoxykanamycin B) was synthesized by H. UMEZAWA and his co-workers 1), based on their theoretical and enzymological studies on the resistance mechanism of the aminoglycoside antibiotics 2). It possesses a prominent activity against the organisms resistant to other aminoglycoside antibiotics and Pseudomonas. Pharmacokinetic studies on this antibiotic in animals and human patients, had been reported by K. UMEMURA and his co-workers.3-6)
The present comunication is concerned with the pharmacokinetic analysis of serum concentration and urinary excretion data from cross-over intramuscular administrations of three dosage levels of dibekacin to healthy male volunteers in Taiwan.

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[in Japanese]

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In the present study, amoxicillin was compared with other antibiotics with respect to sensitivity, levels achieved in the blood and various organs and clinical results. We would like to make further studies accumulated number of cases.

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S-6437 is granule of sustained-release cephalexin which is prepared as longer acting cephalexin. Each gram of the granule contains 200 mg of cephalexin.
Absorption and excretion study of this preparation was performed in 8 patients (3 school children, 3 infants and 2 babies). Mean blood levels of cephalexin following a single oral administration of 25 mg/kg in the school children, for instance, were 1.73, 2.47, 3.11, 2.28, 3.84 and 2.86 mcg/ml at 0.5, 1.0, 2.0, 4.0, 6.0 and 8.0 hours, respectively.
Fifty-two patients with acute respiratory tract infections were treated with this preparation and out of the 52, 33 were evaluable cases. The daily dose used was 50 mg/kg divided in two doses.
Of the 33 patients 29 responded to this preparation showing 87.8% of effectiveness. Four patients who did not respond were 1 with acute pharyngitis, 2 with acute tonsillitis, and 1 with acute bronchitis.
No severe side effects due to this preparation were observed.

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Clinical study of sustained release cephalexin (granules, 200mg/g, S-6437) was conducted in pediatric patients as follows:
1. For infants under 20kg of body weight, 25-50mg/kg/day of this preparation (or 50-100mg/kg/day for severe diseases) were given in two divided doses, and for infants over 20kg, 1g (or 2g for severe diseases) were administered at two divided doses.
2. Patients treated with this preparation were 27 cases with scarlet fever, 3 with acute pharyngitis, 2 with acute tonsillitis, 1 with acute laryngitis, 1 with acute cystitis and 1 with acute enteritis.
3. Out of the 35 patients, 11 showed “very good” response to this preparation, 18 “good”, 3 “fair”, 1 “poor”, and 2 “unknown” indicating 87.9% of effectiveness.
4. Side effects of cheilitis in one patient and vomiting in 1 were observed, and other 2 patients had difficulty in taking this preparation. No other side effects were found.

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Clinical study of S-6437 was performed in 79 patients (31 with scarlet fever, 25 with upper respiratory tract infections and 23 with lower respiratory tract infections). S-6437 was orally administered to the patients with the dose level of 25 to 70mg/kg/day in one or two divided doses. The following is the brief summary of the study.
1. As compared to regular cephalexin, peak blood level of S-6437 was lower and tended to be delayed. Its blood level at 6 hours, however, was about 20 to 30 times higher than that of regular cephalexin.
2.Urinary recovery of S-6437 was as good as that of regular cephalexin.
3. All of 21 patients with scarlet fever who received S-6437 twice a day responded satisfactorily to the drug. The other 10 who were given it once a day also showed good response.
4. Out of 25 patients with upper respiratory tract infections who received 22 to 50mg/kg/day of S-6437 for 2-11 days, 20 showed “very good” response, and 4 “good”.
5.About 30 to 70mg/kg/day of S-6437 were given to 23 patients with lower respiratory tract infections for 5 to 12 days with the following results: “very good”in 12, and “good”in 10.
6. Incidence of side effects (gastrointestinal disturbance) was about 0.5%. No abnormalities in hepatic and renal function tests were observed.
7. In total, 79 patients were studied and the results were as follows: “very good” in 60,“good” in 16 and “unknown” in 3. Effectiveness was about 96%.
From the results, it has been recognized that the sustained release cephalexin is useful in reducing frequency of the administration.

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Clinical and laboratory studies on S-6437 were made, and the following results were obtained.
1. Thirty pediatric patients with various types of infections such as tonsillitis, bronchitis, pneumonia, cystitis, pyelitis, lymphadenitis colli and pyodermia were treated with S-6437 at the daily dosage of 50mg/kg orally, the clinical effectiveness was 89.3%
2. The peak blood level of cephalexin after a single oral administration (25mg/kg) was observed after 4 hours and the average peak blood level of 10 cases was 7.4μg/ml.
3. The average urinary excretion rate of 5 cases was 71.2%.
4. Mild side effects were noticed in a few cases.

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S-6437 was orally given to 29 patients of 3 months to 12 years and 6 months of age who had or urinary tract infections. The daily dose used was 25 to 60mg/kg divided in two doses. The following is the results of this study:
1. With 25-60mg/kg/day, satisfactory results were obtained for upper respiratory tract infections. In lower respiratory tract infections, however, the effectiveness seemed not to be so good as that in upper respiratory tract infections.
2. Side effects such as diarrhea, loose stool, abdominal pain and eruption were observed but they were temporary. Therefore, the administration of S-6437 was not discontinued due to such side effects.
3. S-6437 was acceptable to elder children but some of children of 2-4 years of age disliked this preparation because it was not smooth in their mouths. Therefore, the preparation of S-6437 should be further improved.
4. Since it has been recognized that blood levels of cephalexin following the administration of S-6437 last for a longer period of time than regular cephalexin, S-6437 is considered to be a useful preparation.
5. B. I. D. and T. I. D. regimens of S-6437 will give clinical satisfaction to children over 6 years and ones under 6 years, respectively.

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In order to clinically evaluate S-6437, the following study was carried out in pediatric patients.
This clinical study was performed in 30 patients ranging from 2 years and one month to 10 years and one month of age. Seven patients had scarlet fever, 3 acute pharyngitis, 4 acute suppurative tonsillitis, 6 acute bronchitis, 2 acute pneumonia, 3 acute pyelonephritis, 1 chronic pyelonephritis, 2 vaginitis, 1 acute gastro-enteritis, and 1 impetigo. The degree of these diseases were all mild or moderate. These patients were orally administered 35-50mg/kg/day in two divided doses for 3 10 days.
As a result, effectiveness of this preparation in these patients was 80% and no side effects were observed.

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Peak blood level of cephalexin was obtained at 4 hours after the administration of S-6437 as opposed to 2 hours after regular cephalexin. Peak blood level with regular cephalexin was higher than that with S-6437. Blood levels with S-6437, however, stayed for longer period than those with regular cephalexin.
Mean urinary recovery within 12 hours after the administration of S-6437 after meal and during meal were 57.1 and 69.3%, respectively.
S-6437 was studied in 23 pediatric patients, 7 with acute tonsillitis, 15 with acute cystitis and 1 with cellulitis. They were orally given 400 to 1,200mg/day of S-6437 in two divided doses at 30 minutes after meal for 4-12 days. Of the 23 patients, 18 responded to the drug but 5 did not respond.
As for side effects, eruption and diarrhea were observed in 1 and 2 patients, respectively. No other side effects were found.

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S-6437 is a newly manufactured cephalexin (CEX) for children and, in order to maintain a longer effective blood concentration of the drug, is so prepared for 30% of the drug to be soluble in the stomach and 70% in the intestine. The results of the fundamental and clinical studies are as follows:
1. Solubility of enteric-soluble part of the drug was low in the rabbit when give orally and its absorption rate was only 30%. Consequently, the rabbit was not considered to be a suitable substitute for a human model for this type of medication.
2. Blood concentrations of the drug after its single oral dose of 25mg/kg in three children was different from one patient to another, but the following mean values were obtained: 2.04 μg/ml (30 minutes), 5.98 (1 hour), 4.9 (2 hours), 3.5 (4 hours), 3.0 (6 hours) and 1.29 (8 hours). The peak concentration of the drug was lower than that of CEX, but maintenance of an effective blood concentration was apparently longer. Its urinary recovery rate was 80.7% up to 12 hours.
3. Ten children with tonsillitis (group A β-hemolytic Streptococcus, 3;Staphylococcus aureus, 4; unknown, 3) and five children with E. coli urinary tract infection were treated with a daily dose of 40-60 mg/kg for 7 days. The clinical effect was excellent in 8, good in 1 and failure in 1 in 10 patients with tonsillitis and excellent in 4 and good in 1 in 5 patients with urinary tract infection. The overall efficacy rate was 93.3%, i. e., excellent in 12, good in 2 and failure in 1.
4. Adverse reactions included rash (1), a transient anemia (1), soft stool (2) and diarrhea (1). They were all mild and temporary and did not preclude further administration.
5. Based on the above results, it is considered that S-6437 is an efficient antibiotic, especially in children, in whom CEX is indicated and besides repeated administration of the drug is difficult.

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In this paper, we studied the ototoxic effects of ribostamycin (vistamycin (VSM)), kanamycin (KM), dibekacin (panimycin (DKB)) and gentamicin (GM) on the inner ear in the spontaneously hypertensive rats (SHR) and Wistar strain rats.
VSM were given at the doses of 500, 400, 200mg/kg, KM at the doses 400, 300, 200mg/kg, DKB at the doses 300, 200mg/kg and GM at the doses of 300, 200, 100mg/kg, respectivelly, and each drug was injected intramuscularly for 45 days.
After the final administration, the animals were sacrificed by decapitation and the skulls including the temporal bones were fixed in 10% formalin. The skulls were decalicified and then dehydrated and embedded in celloidin.
Serial horizontal celloidin sections were prepared and stained with hematoxylin-eosin.
(1) SHR group.
Two of the rats treated with VSM 500mg/kg, one with DKB 300mg/kg, two with DKB 200mg/kg and five with GM 300 and 200mg/kg, died during the course of experiment, but the remaining rats in these groups were alive until the end of experiment.
Histologically, the loss of the outer hair cells of the organ of CORTI in SHR did not occur in any of the rats received KM, VSM and DKB, except one of the SHR given GM 300mg/kg for 45 days.
(2) Wistar rats group.
Two of the rats treated with VSM 500mg/kg, DKB 300 mg/kg and GM 200 mg/kg respectively and all of the rats treated with GM 300mg/kg died during the course of the experiment but the remaining animals in each group were alive.
Histopathologically, there was no remarkable damage in the organ of CORTI in all the rats treated with VSM, DKB 200mg/kg and GM 100mg/kg. Three of the rats treated with KM 400mg/kg, two with KM 300mg/kg and DKB 300mg/kg, four with KM 200mg/kg and GM 200mg/kg showed the loss of outer hair cells extending from the basal end to the partial part of second turn of the cochlea.

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[in Japanese]

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[in Japanese]

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