ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF ¹⁴C-AC-1370 IN RATS AFTER INTRAVENOUS ADMINISTRATION

Abstract

Absorption, distribution, metabolism and excretion of AC-1370 were studied in rats after single or repeated intravenous administration of ¹⁴C-AC-1370 to Fischer rats.
1) After intravenous administration of ¹⁴C-AC-1370, biphasic decrease of the radioactivity in the plasma was observed. Plasma half life at the dose of 30mg/kg was 22 min. C₀ and AUC were increased in proportion to the increase of dosage (30-200mg/kg), while T1/2 and kel did not change.
2) After single intravenous injection, the tissue level of radioactivity was highest in the kidney followed by plasma, lung, skin, liver, heart, spleen and thymus. The radioactivity in the brain and the spinal cord was very low. Only a small amount of radioactivity passed through the placenta, and the transfer to the milk was also small.
3) Within 72 hr after single intravenous injection, 84% and 9% of the given radioactivity were excreted in the urine and feces, respectively. About 4% of the doses was excreted in the bile within 24 hr.
4) No metabolites were detected in the plasma at 15 and 30 min after injection and in the 2 and 6 hr pooled urine.
5) Upon repeated intravenous administration twice a day, the radioactivity in the tissue increased gradually and plateaued at the 5th to the 9th administration. The radioactivity in theplasma after multiple injections was similar to that of the 1st administration. Distribution patterns of radioactivity after repeated administration were almost the same as that of a single administration. Excretion rates of radioactivity in the urine and feces were nearly constant during repeated administration.