1984 Volume 32 Issue Supplement2 Pages 133-151
The disposition and metabolism of TA-058, a new semisynthetic penicillin, were studied in mice and rats.
1) The plasma half-lives of radioactivity in mice and rats after intramuscular injection of 3H-TA-058 (20mg/kg) were 17 and 18 minutes
The tissue levels in both animals were highest at about 15 minutes after the injection. The kidney, liver, lung and plasma showed high concentrations of radioactivity while the brain had the lowest level.
2) When 14C-TA-058 (20mg/kg) was injected intravenously, the tissue levels in rats were similar to those obtained after intramuscular injection of 3H-or 14C-TA-058.
3) In the whole body autoradiograms of mice and rats after intravenous injection of 14C-TA-058 (20mg/kg), considerable radioactivities were observed in the kidney, liver, lung, subcutaneous connective tissue and oral and nasal mucosa.
4) The urinary excretion rates of radioactivity in mice and rats were about 83% and about 72% of the dose, respectively, within 72 hours after intramuscular injection of 3H-TA-058 (20 mg/kg and 100mg/kg) and the fecal excretion of radioactivity was about 15% in mice and about 24% in rats in the same period. Most of the urinary radioactivity was excreted within 4 hours after administration.
The urinary excretion rates obtained by radioassay and bioassay were nearly equal in both animals, but no antibacterial activity was found in the feces of both animals.
5) After intravenous and intramuscular injection of 14C-TA-058 (20mg/kg) to rats, the radioactivity excreted within 72 hours was about 70% of the dose in the urine and about 28% in the feces, and there was no sex difference in either urinary or fecal excretion.
When 14C-TA-058 (20mg/kg) was injected intramuscularly to rats, the radioactivity excreted into the bile and that expired as 14CO2 were 30% and 0.05% of the dose, respectively.
6) Within 6 hours after intramuscular injection of 14C-TA-058 to rats, most of the radioactivity excreted in the urine and bile was intact TA-058, and the rest consisted mainly of penicilloic acid and a dimer of TA-058.
7) When 14C-TA-058 (20mg/kg) was injected intramuscularly to pregnant rats at the late stage of gestation, the radioactivity in the fetus was 0.083% of the dose at 60 minutes and it became undetectable at 8 hours.
No or very low radioactivity was found in the tissues of suckling rats when the dam rats were intramuscularly injected with 14C-TA-058.
8) When 14C-TA-058 (50 mg/kg) was injected intramuscularly to rats once daily for 6 days, the radioactivity in each tissue at 24 hours after the last administration was only 1.1-2.0 times higher than that after single administration and no tendency of tissue accumulation of the radioactivty was recognized.
