A NEW ANTIBIOTIC, JOSAMYCIN. VI ABSORPTION AND DISTRIBUTION OF JOSAMYCIN

Abstract

Following oral administration of 100mg/kg each of four macrolides, josamycin, erythromycin, leucomycin and spiramycin, their serum levels in dogs were determined microbiologically. The serum level of josamycin was 26.2mcg/ml and 31.0mcg/ml 1 hour and 2 hours after administration, respectively. By these times josamycin and spiramycin gave higher levels than erythromycin and leucomycin. However, by 8 and 24 hours after administration spiramycin gave the highest level among them.
In the experiment on mice, tritiated josamycin at the dose of 200mg/kg was given orally and distribution of the radioactivity and of the antibacterial activity in tissues was determined. By 1 hour after administration, 47% of the radioactivity was recovered in the intestine, 17% in the urine, 3.2% in the liver and 2.4% in the bile. The radioactivity per unit weight was highest in the bile, followed by the small intestine, large intestine, feces, stomach and liver in that order. By 3 hours after administration, 42% was found in the intestine, 26% in the urine, 8.5% in the lungs, 3.3% in the liver, 3.2% in the muscles and 1.3% in the heart. The radioactivity per unit weight was highest in the lungs, then it decreased in the order heart > bile > thymus > feces > large intestine > liver > small intestine > kidney and stomach. Recovery rates of total radioactivity at 1 and 3 hours after administration were 73% and 88% respectively. Distribution of josamycin in plasma, urine and several organs as computed from the data obtained by radioactivity and antibacterial activity went parallel, but the former gave much larger figures than the latter.
The above data lead to the conclusion that josamycin is readily absorbed from the digestive tract, but decomposed relatively fast, losing its antibacterial activity.