[Absorption, distribution, metabolism and excretion of netilmicin in rats (III). Metabolic fate of 14C-netilmicin after intramuscular administration (author's transl)].

The metabolic fate of 14C-netilmicin (14C-NTL) was studied in rats after intramuscular administration (20 mg/kg). 1. Binding ratio of 14C-NTL to rat plasma protein, determined by the ultracentrifugal method, was 15 approximately 20% during the first 1 hour after intramuscular administration. 2. Binding ratio of 14C-NTL to HSA, determined by the equilibrium dialysis method, was 15 approximately 23%. Binding constant (K) and maximum binding number (n) were calculated as 1.48 X 10(4) and 3.3 mole/mole, respectively. Half of 14C-NTL bound to HSA was dissociated from HSA by gel-filtration. 3. The radioactivity in tail vein blood reached peak level at 10 minutes after intramuscular administration and declined rapidly. 4. Since the distribution rate of 14C-NTL into the blood cells was low during the first 2 hours, the plasma level at that time was about 1.5 times higher than whole blood level. 5. The recovery of radioactivity in the bile (0 approximately 24 hours) was only 0.13% of the dose administered. An average concentration during 2 hours after intramuscular injection was 2.5 mcg/ml. 6. Within 2 hours after administration, approximately 40% of the dose was recovered in the urine. Within 24 hours, 87.8% of the dose was excreted in the urine, 2.6% in the feces, 0.3% in the cage washing and 8.8% in the carcass. Total recovery ratio was 99.5% of the dose. 7. The radioactivity was widely distributed in the tissues, especially high in the kidney and bone, low in the brain. A high concentration of radioactivity was found in the renal cortex at 24 hours after administration. 8. Netilmicin was excreted into the urine unchanged and no metabolites were detected by TLC at all.