Tissue distribution of macromolecular conjugate, adriamycin linked to oxidized dextran, in rat and mouse bearing tumor cells
| Autor: | Norihide Kishi, Kouichi Yamanouchi, Yasuo Ueda, Kazumasa Yokoyama, Yoshiyasu Kawabata, Yoshihisa Sogame, Koji Munechika |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Lung Neoplasms Ratón Cell Transplantation Pharmaceutical Science Excretion chemistry.chemical_compound Feces Mice Internal medicine medicine Distribution (pharmacology) Animals Doxorubicin Tissue Distribution Carcinoma 256 Walker Rats Wistar Pharmacology Mice Inbred BALB C Chemistry Lewis lung carcinoma Dextrans General Medicine Rats Endocrinology Dextran Immunology Chromatography Gel Drug carrier Neoplasm Transplantation medicine.drug Conjugate |
| Zdroj: | Biologicalpharmaceutical bulletin. 17(9) |
| ISSN: | 0918-6158 |
| Popis: | Tissue distribution of the radioactivities after intravenous administration of [14C] adriamycin ([14C] ADM) or [14C] ADM linked to oxidized dextran ([14C] ADM-OXD) in mouse bearing Lewis lung carcinoma (LLC) and rat bearing Walker 256 carcinosarcoma was studied. ADM conjugated with OXD increased plasma half-life and gave high area under the plasma concentration-time curve (AUC). The AUC values were 13.0 and 5.8 times higher than those of the [14C] ADM group in mice and rats, respectively. In the tumor tissues, AUC values of the [14C] ADM-OXD group were also respectively 1.6 and 1.9 times higher than those of the [14C] ADM group. However, the AUC values in the heart of the [14C] ADM-OXD group were about half those of [14C] ADM group in both animals. Thus the distribution of ADM was changed by the conjugation with OXD. The excretion profile of ADM was also changed by the conjugation. During 6h after administration, [14C] ADM-OXD was mainly excreted into rat urine at 45.2% of the original dose, but in the [14C] ADM group recovery in urinary excretion was 4.2%. Using [14C] ADM-OXD and ADM-[14C] OXD, the respective tissue distribution of ADM and OXD portions in the ADM-OXD was studied in rats bearing Walker 256. The radioactivities of both [14C] ADM-OXD and ADM-[14C] OXD groups increased in tumor and liver within 1h after administration. In the liver, both radioactivities were retained for 24h, which suggested that ADM and OXD were retained as conjugated form, however, different behavior was observed between the two groups in tumor tissues. Peak [14C] ADM-OXD radioactivity was reached 6h after administration and then decreased, while, ADM-[14C] OXD was quickly cleared from the tumor after 1h administration. The results suggested that ADM was released from ADM-OXD and the remaining ADM-OXD, which was low in ADM content, was then cleared from the tumor tissues. |
| Databáze: | OpenAIRE |
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