Pharmacokinetical change of adriamycin by the conjugation with DIVEMA(a copolymer of divinyl ether and maleic anhydride)

• Published in: Drug Delivery System Vol. 6; no. 1; pp. 51 - 56
• Main Authors: Ueda, Hiroshi, Hirano, Takashi, Todoroki, Takeshi, Ohashi, Shinichi, Kawai, Yuichi, Tsukagoshi, Shigeru, Iwasaki, Yoji
• Format: Journal Article
• Language: Japanese
• Published: THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM 10.01.1991
• Subjects: adriamycin(ADR); conjugate; DIVEMA; pharmacokinetics
• ISSN: 0913-5006; 1881-2732
• DOI: 10.2745/dds.6.51

Adriamycin (ADR) was covalently conjugated with a copolymer of divinyl ether and maleic anhydride (DIVEMA). Either sole ADR or DIVEMA-ADR conjugate was injected intraperitoneally into mice, and the concentration of ADR in the serum and peritoneal fluid (PF) was measured by HPLC (high-performance liquid chromatography). A reversed phase liquid chromatography column enabled to measure the concentration of ADR as low as 6 ng/ml. In sole ADR administration, the ADR concentration in the PF reached 179 ng/ml at one hour then gradually decreased to 13 ng/ml at 24 hours after i.p. injection. In contrast, the concentration in the serum fell rapidly from 16.8 ng/ml at one hour to 6.6 ng/ml at 2 hours after the injection. In DIVEMA-ADR conjugate, the ADR concentration in the PF was elevated to 4, 057 ng/ml at one hour and decreased more slowly than in sole ADR. Even at 24 hours after i.p. administration of the conjugate, ADR was kept as high as 90 ng/ml in the PF. On the other hand, the serum concentration remained under the limit of detection at all times measured. Pharmacokinetic parameters were obtained based on the time-concentration curves of either sole ADR or DIVEMA-ADR administration, using two-compartment model. The results showed that the conjugate increased the AUC(area under the curve) of ADR in the PF by 15.4 times higher than that of sole ADR. These remarkable ability of DIVEMA conjugate on pharmacokinetics of ADR would be greatly contributable for improvement of cancer chemotherapy, especially for the treatment of peritoneal dissemination from intraabdominal malignancies.