[Pharmacokinetic studies of THP-ADM (tetrahydropyranyl adriamycin)]

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. Short t1/2 was noted compared with that of Adriamycin in a 3-compartment open model. Leukocyte concentration of THP-ADM was much higher than that of plasma or red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. Tissue concentration revealed high THP-ADM and low Adriamycin in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. The Adriamycin was most likely related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue or both. Poor penetration of THP-ADM was noted into the third space.