1996年10月
Pharmacokinetic analysis of drug disposition after intratumoral injection in a tissue-isolated tumor perfusion system
PHARMACEUTICAL RESEARCH
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- 巻
- 13
- 号
- 10
- 開始ページ
- 1438
- 終了ページ
- 1444
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1023/A:1016054807555
- 出版者・発行元
- PLENUM PUBL CORP
Purpose. The purpose of this study was to establish an experimental system for evaluation of the intratumoral behavior of drugs after intratumoral injection using perfused tissue-isolated tumor preparations of Walker 256 carcinoma (3.46-9.73 g, n = 16). Methods. We quantified the recovery of Phenol Red (model drug) in the tumor, leakage from the tumor surface and the venous outflow after intratumoral injection using perfused tissue-isolated tumors, and analyzed venous appearance curves based on a pharmacokinetic model in which the tumor tissue was assumed to be divided into two compartments, i.e., well- and poorly-perfused regions. Results. In small tumors (Type 1, 5.42 +/- 0.39 g), the drug appeared immediately in the venous outflow, and the amount remaining in the tumor tissue at 2 hr after injection was small. In contrast, the venous appearance rate reached a significantly lower peak a few minutes after injection, and a large amount of injected drug remained in some large tumors (Type 2, 8.17 +/- 0.51 g). Pharmacokinetic analysis revealed that there was a correlation between tumor weight and the rate constants of transfer from the poorly-perfused region to the well-perfused region, and between the rare constants of transfer from the well-perfused region to the venous outflow and dosing ratios into the well-perfused region. Conclusions. An experimental system and analytical method were established for the evaluation of the intratumoral behavior of drugs after intratumoral injection using a tissue-isolated tumor perfusion system. This experimental system will be useful in analyzing the antitumor drug disposition after intratumoral injection.
- リンク情報
- ID情報
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- DOI : 10.1023/A:1016054807555
- ISSN : 0724-8741
- PubMed ID : 8899832
- Web of Science ID : WOS:A1996VN25700003