[in Japanese]

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Laboratory and clinical investigations were made on clindamycin-2-phosphate, and the following results were obtained.
1. Antibacterial activity: Clindamycin-2-phosphate and clindamycin-2-palmitate both showed MICs of more than 100μ/ml against Staphylococci and Streptococci; on the other hand, clindamycin and N-demethyl-clindamycin inhibited these bacteria at concentrations of less than 0.05μ/ml, and clindamycin sulfoxide did so at concentrations of more than 6.25μ/ml. For most of gram-negative bacilli, the MICs of these four analogs were above 100μg/ml.
2. Sensitivity of clinical isolates of Staph. aureus: When clindamycin and N-demethyl-clindamycin were tested against 54 strains of clinical isolates of Staph. aureus, the number of strains sensitive to them reached the peak at a concentration of 0.1μ/ml, while that of strains sensitive to clindamycin sulfoxide was the largest at 1.56μ/ml. However, 19 strains were resistant to more than 100μ/ml of these three antibiotics. The MICs of clindamycin-2-phosphate and clindamycin-2-palmitate were above 100μ/ml against all of the 54 strains of Staph. aureus tested. Cross-resistance developed between clindamycin and N-demethyl-clindamycin.
3. Blood and salivary levels and urinary excretion: The subjects each receiving a single intramuscular dose of 600 mg of clindamycin-2-phosphate showed peak blood levels at 30 minutes, averaging 7.43μ/ml. At 1, 2, 4 and 6 hours after administration, average blood levels were 6.68, 4.95, 3.58 and 2.55μ/ml, respectively. Urinary excretion of the drug was simultaneously determined in the same subjects, and peak urinary levels were reached at 1 hour after dosing, with an average of 331.25μ/ml. The average urinary recovery within 6 hours was 9.1% in these subjects.
Following a single 600 mg dose of clindamycin-2-phosphate by intravenous route, blood levels peaked at 15 minutes, averaging 10.29μ/ml. The 1/2, 1, 2, 4 and 6 hours values were 7.97, 5.82, 4.77, 3.67 and 2.68μ/ml, respectively. Thirty minutes following this dosing, peak urinary levels were attained with an average of 773.3μ/ml. The urinary recovery within 6 hours was found to be 15.59%. The average level of the drug in saliva reached the peak of 3.57μ/ml at half an hour following the intravenous dosing of 600 mg.
4. Tissue concentrations: Tissue concentrations of clindamycin-2-phosphate were determined in three rats of SD strain given a single dose of 20 mg/kg intramuscularly. Lung showed the highest level, followed by liver, kidney, spleen, serum, heart and brain.
5. In vivo metabolism: The in vivo metabolism of clindamycin-2-phosphate was studied by thinlayer chromatography, and the drug was found to be metabolized into clindamycin, N-demethylclindamycin and clindamycin sulfoxide.
6. Clinical investigation: Eight surgical cases were treated with clindamycin-2-phosphate, and one was excluded from evaluation because the drug was administered for prophylactic purposes. The drug was found effective in 5 of 7 patients. No patient developed adverse effects associated with the antibiotic.

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Cephaloridine (CER) concentration in the bone marrow of tibia was examined 1, 2, and 3 hours after intramuscular injection of 1 g. CER concentration in the bone marrow of tibia 1 hour after injection was 26.0±8.927μg/ml. Ratio to serum was 78.5%. CER concentration in the bone marrow of tibia 2 hours after injection was 20.6=0.003μg/ml. Ratio to serum was 87.3%. CER concentration of bone marrow of tibia 3 hours after injection was 14.8±4.791μg/ml. Ratio to serum was 91.9%. Difference of concentration between in bone marrow and serum was not statistically significant. Penetration capacity of CER into the bone marrow of tibia was excellent.

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Neuromuscular blocking properties of tobramycin (Tobracin IP 60 mg), dibekacin (Panimycin® 100 mg) and ribostamycin (Vistamyciwit, 1g) were studied in man during anesthesia and surgery by observing the effects of these antibiotics on muscle twitch tension.
These antibiotics alone did not show any neuromuscular blocking action in the therapeutic doses. The neuromuscular blocking action of d-tubocurarine chloride was potentiated by the intravenous administration of 1g of ribostamycin. Tobramycin 60 mg did not show any remarkable effect, but dibekacin 100 mg produced a slight potentiating effect on the action of d-tubocurarine. The enhancement of the action of d-tubocurarine was antagonized by edrophonium and calcium. The action of succinylcholine chloride was not affected by tobramycin or ribostamycin, but it was potentiated transitorily by dibekacin.
It is advisable to pay attention to possible respiratory depression when ribostamycin and dibekacin are used in combination with non-depolarizing muscle relaxants and/or anesthetics.

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Non-antimicrobial actions of oleandomycin (triacetyloleandomycin and oleandomycin phosphate) were studied in patients with bronchial asthma. Twenty-one cases of the disease without associating infections entered the study, and they were given 750 mg of oleandomycin or triacetyloleandomycin in three divided doses daily for two weeks. Clinical manifestations and laboratory findings were compared to assess the effectiveness of the antibiotic therapy between the three 2-week periods before, during and after the therapy. Improvements in clinical manifestations were attained in 11 of 21 cases (52.3%), and lasted after discontinuance of the therapy in 8 (38.1%). The blood level of 11-OHCS as determined by the DEMOOR'S fluorescence method increased by greater than 20% at the end of therapy in 7 of 18 cases (38.9%). In 5 of the 7 cases favorable responses were seen clinically to the oleandomycin therapy. The serum IgE level determined by the radioitnmunosorbent test was compared before and after the therapy to reveal that oleandomycin caused decrease of IgE in 10 and increase in 9 of 20 cases examined. The oleandomycin therapy resulted increases by greater than 20% of the vital capacity and FEV1.0 in 2 and 3, respectively, of 15 cases. Jaundice in association with elevations of the GOT, GPT and alkaline phosphatase developed in one patient, and generalized skin eruption in another. Both of these cases were given triacetyloleandomycin.

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