Abstract
Laboratory and clinical studies were carried out on 9, 3-diacetylmidecamycin(MOM), and the following results were obtained.
(1) In vitro tests
The antibacterial activity of MOM was determined against S. aureus and S.pyogenes each 54 strains, and comparison was made with the activities of EM, MDM and CEX.To MOM when the undiluted culture broth was used, the sensitivity peak of S.aureus, was found to occur in the range of0.39-0.78μg/ml, while the peak occurred at0.39μg/ml when the 100-fold dilution of the culture broth was employed. EM and MDM showed low MIC values in a small number of the S.aureus and their sensitivity distribution patterns were similar to that seen with MOM. With MOM, 11strains showed MICs of50μg/ml or more, while there were20such strains for MDM and25for EM.
Comparison with CEX, on the other hand, showed that, when using the undiluted culture broths of the test strains as the inocula, the activity of MOM was superior by3tubes. When the100-fold dilutions of the broths were employed, however, the reverse was true: The results with CEX were superior by about 1 tube.
The plot of the results of MOM in vitro activity against S. pyogenes revealed a wide distribution of MICs from0.05 to ≥100μg/ml when the undiluted culture broths were employed as the inocula. The curve showed2peaks of sensitivity: at0.1μg/ml and25μg/ml.When the100-fold dilutions of the culture broths were used, the MIC distribution was from0.05 to12.5μg/ml, with a sensitivity peak occurring at0.1μg/ml.In comparison with the other3test antibiotics, these results with MOM were slightly inferior.
(2) Absorption and distribution studies
Eight subjects, ranging in age from5to14years, were used in this study. At2hours after eating, these subjects were orally administered MOM in a dose of20mg/kg (3 subjects), 15mg/kg (2 subjects) or10mg/kg (3 subjects). The concentration of MOM in the serum was then monitored. In the20mg/kg administration group, the MOM serum concentration was 0.55μg/ml at 1 hour, 1.3μg/ml at2hours, 1.11μg/ml at3hours, 0.68μg/ml at4hours and not detectable at6hours. Similarly, in the15mg/kg administration group, the MOM serum concentration was0.60μg/ml at1hour, 0.59μg/ml at2hours and0.44μg/ml at4hours. In the10mg/kg dosage group, MOM serum concentrations was0.54, 0.48 g/ml and0.32μg/ml at1, 2and4hours. There were somemoderate differences between there3MOM administration groups in terms of the time of the peak serum concentration and the slope of the concentration decrease, but they did show a dose response.
The urinary recovery rate during the6-hour period following the dosing was found to range from 1.24to4.24%in the20mg/kg MOM dosage group. The corresponding value was between 0.96 and 1.89%in the15mg/kg dosage group and0.73to1.87%in the10mg/kg dosage group.
In another study, 6subjects were used;they ranged in age from4to16years. MOM was administered to these subjects in the early morning when they were in a fasting state. The dosage levels were20mg/kg and10mg/kg, and the transfer of the drug to the serum was measured. In the20mg/ kg dosage group, the MOM serum concentrations were found to be1.75μg/ml at1hour, 2.60μg/ml at 2hours, 1.61μg/ml at4hours and0.73μg/ml at6hours. The10mg/kg dosage group was found to show concentrations of1.95μg/mi at1hour, 0.73μg/ml at2hours, 0.47μg/ml at4hours and0.40μg/ml at6hours. In the previous study, when the subjects were administered MOM after a meal, MOM could not be detected in the serum at6hours after the dosing, but in these fasting subjects even the 6-hour serum concentration was higher than the4-hour concentration in the non-fasted subjects. The urinary recovery rate was determined for the 3 subjects who were administered MOM at20mg/kg in this study;their individual 6-hour values were1.97, 4.37% and 4.79%, which are in fact rather low.
