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The 14C-labelled compound of FK037 (14C-FK037), a new antibiotics, was intravenously administered in male rats at a dose of 20 mg/kg once a day for 14 days, and its distribution, metabolism and excretion were investigated.1. The radioactivity in the blood collected at 8 hr after 1st, 2nd, 10th and 14th dosing was as follows n.d. (not detected), 0.24, 0.42 and 0.43 μg eq./ml, respectively and attained the steady state after the 10th dosing. The area under the blood concentration-time curves up to infinite (AUC0-∞, 22.6μg eq.·hr/ml) after single intravenous administration was similar to AUC0-24hr after 7th and 14th dosing (19.2 and 24.4μg eq.·hr/ml, respectively).2. Tissue levels of radioactivity in most of tissues at 8 hr after each dosing increased according to the multiple intravenous dosing for 14 days. The radioactivity in the tissues such as kidney, skin, bladder, stomach, lung, brown fat, skeletal muscle, prostate gland and parotid gland at 8 hr after the final dosing was 3.1-5.5 times higher than those at 8 hr after the 1st dosing. The radioactivity in other tissues at 8 hr after the final dosing was 2 times higher than those at 8 hr after the 1st dosing. Tissue concentration of radioactivity at 24 hr after the final dosing was less than 4% of those at 5 min after the final dosing.3. During the multiple intravenous dosing of 14C-FK037, the ratios of unchanged FK037 and metabolites in plasma and urine were not changed. The most of radioactivity in plasma and urine consisted of the unchanged FK037.4. During the multiple intravenous dosing of 14C-FK037, the ratios of urinary and fecal excretion of radioactivity were not changed. The urinary excretion of radioactivity was 94.2 and 94.3% of cumulative doses at 24 and 120 hr after the final dosing, respectively.

Disposition of FK037. (2). Distribution, Metabolism and Excretion of FK037 in Rats after Multiple Intravenous Dosing.