PHARMACOKINETICS AND DISPOSITION OF A NEW ANTITUMOR ANTIBIOTIC (2R)-4'-O-TETRAHYDROPYRANYLADRIAMYCIN IN RATS DISTRIBUTION AND EXCRETION AFTER MULTIPLE ADMINISTRATION

• Published in: Japanese journal of antibiotics Vol. 39; no. 2; pp. 629 - 637
• Main Authors: TONE, HIROSHI, IGUCHI, HIROSHI, SHOMURA, TOMOKO, KOMIYA, IZUMI, NISHIO, MOTOHIRO
• Format: Journal Article
• Language: Japanese
• Published: Japan Japan Antibiotics Research Association 01.02.1986
• Subjects: Aminopyrine N-Demethylase - biosynthesis; Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - metabolism; Antibiotics, Antineoplastic - toxicity; Doxorubicin - administration & dosage; Doxorubicin - analogs & derivatives; Doxorubicin - metabolism; Doxorubicin - toxicity; Enzyme Induction - drug effects; Injections, Intravenous; Kinetics; Male; Rats; Rats, Inbred Strains; Tissue Distribution
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.39.629

The accumulation of (2R)-4'-O-tetrahydropyranyladriamycin (THP) was studied in rats received intravenous administration of 14C-THP at a dose of 0.5mg/kg/day for 14 consecutive days by determining blood and tissue levels and the excretion of the radioactivity. The radioactivity levels in plasma and blood cells after the multiple administration were higher than those after single administration. The half-life of the radioactivity after the multiple administration was longer in the blood cells but not in the plasma than the half-life after a single administration. Tissue levels of the radioactivity after the multiple injection were 2 to 4 times as high as the levels after a single injection except for the brain and testes in which a large accumulation of the radioactivity was observed. However, little accumulation of unlabeled THP was found in most tissues when determined by HPLC. The accumulation of radioactivity in tissues, therefore, was due to metabolites of THP. The disposition of 14C-THP was also examined in rats which had previously received unlabeled THP (0.5mg/kg/day) for 13 days. The pretreatment did not affect the disposition of 14C-THP seriously, although the pretreatment raised tissue levels slightly and a rebound of plasma level of 14C-THP, and lowered the fecal excretion ratio. No induction of hepatic drug metabolizing enzymes was observed in rats after repeated administrations of THP for consecutive 14 days.