Pharmacokinetics of doxorubicin, (2"R)-4'-O-tetrahydropyranyl-adriamycin and aclarubicin.

  • 1 May 1986
    • journal article
    • research article
    • Vol. 39 (5), 1321-36
Abstract
The following paragraphs summarize the properties of ADR, THP and ACR in terms of their pharmacokinetics. The blood level of anthracyclines shows a three-phase function of decline: alpha, beta and gamma phases. Compared with other classes of anticancer agents, the anthracyclines are characterized by an extremely short T1/2(alpha) and an extremely long T1/2(gamma). These characteristics reflect the facts that anthracyclines are rapidly transferred to the tissues and that they are retained for a long time in the body. In comparison with ADR, the T1/2(alpha) of THP is relatively short and T1/2(alpha, beta and gamma) of ACR are also short. Anthracyclines show large values for K12 and K13, transfer rate constants of the drug from the blood to the tissues, and small values for K21 and K31 transfer rate constants of the drug from the tissues to the blood. This means that these drugs are rapidly transferred to the tissues, from which they are then slowly released. The order of magnitude of K12 and K13 was THP greater than ACR greater than ADR. The order for K21 and K31 was ACR greater than THP greater than ADR. Anthracyclines are also characterized by small distribution volumes (V1) in the blood circulation, and very large distribution volumes (V2 and V3) in the tissue compartments. The order of magnitude for V2 and V3 was THP greater than ADR greater than ACR. Anthracyclines achieved high concentrations in such thoracic and abdominal organs such as lung, heart, thymus, liver, kidney, spleen and digestive tract. ADR showed the highest levels in liver and kidney, while THP and ACR showed their highest concentrations in lung and spleen. A decrease in the drug concentration in various organs is slow in the case of ADR, while rapid in the cases of THP and ACR. Most of the distributed drug is the unchanged form with ADR, whereas metabolites are common with ACR. THP is partially converted to ADR in liver. Anthracyclines were usually excreted over a long period of time at a high rate in the bile and at a low rate in the urine. Orally-administered ACR showed considerably good absorption from the digestive tract. The metabolism of anthracyclines was carried out in vivo and resulted in the formation of bioactive glycoside metabolites and inactive aglycone metabolites.(ABSTRACT TRUNCATED AT 400 WORDS)