On a new tetracycline derivative, minocycline, several basic and clinical studies were performed an the following results were obtained.
1. The sensitivity of strains of
Staphylococcus aureus to minocycline was excellent, even though the strains were resistant to tetracycline. However in case of Gram-negative bacilli there was no clear difference in sensitivity to both tetracyclines.
2. The mode of antibacterial action of minocycline was considered to be chiefly bacteriostatic.
3. In experimental staphylococcal infections of mice, good results were obtained with minocycline corresponding to its small M. I. C. values.
4. Mean serum level following oral administration of minocycline to seven healthy men reached to about 1.2mcg/ml at peak after 3 hours,keeping the value of 1 mcg/ml at 6 hours from starting. Serum level studies after the administration, the initial dose of 200mg was followed by 100mg every 12 hours, revealed neither marked reduction nor excessive accumulation.
5. Urinary recovery rate was as low as 6. 1% in 12 hours.
6. Fecal concentration ranged from 10 to 40mcg/g in general.
7. When urinary and fecal recovery rates were calculated 104 hours after single 200mg oral administration of minocycline to 5 healthy adults, the former was 22.8%, the latter 3% in an average, amounting to 25.8% only in total.
8. Bile and urinary levels after oral administration to dogs were similarly high, being 10-30 folds of serum ones.
9. Peak values of each tissue level following oral administration to mice were ranked in order of liver, spleen, lung and kidney.The reduction of activity was observed by homogenizing tissues and remaining rate was 30 to 40% of calculated values in all tissues.
10. Four metalic ions of Ca, Mg,Al and Fe inactivated minocycline to the same extent as tetracycline.
11. Clinically,4 cases with respiratory infections,3 with pyelitis and one with colitis,received minocycline. Minocycline was judged to be effective with one exception of pyelitis case.
12. In one case,after 4 doses of each 100mg in every 12 hours, dizziness and nausea appeared andsubsided in 24 hours after stopping the administration.
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