Pharmacokinetic analysis of drug disposition after intratumoral injection in a tissue-isolated tumor perfusion system.

Abstract

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 (3.46-9.73g, 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 rate 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.

• Authors: A Saikawa, T Nomura, F Yamashita, Y Takakura, H Sezaki, M Hashida
• Journal: Pharmaceutical research (Pharm Res) Vol. 13 Issue 10 Pg. 1438-44 (Oct 1996) ISSN: 0724-8741 [Print] United States
• PMID: 8899832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serum Albumin, Bovine
• Evans Blue
• Phenolsulfonphthalein

Topics

• Animals
• Carcinoma 256, Walker (blood supply, metabolism)
• Drug Screening Assays, Antitumor
• Evans Blue (administration & dosage, pharmacokinetics)
• Female
• Injections, Intralesional
• Perfusion
• Phenolsulfonphthalein (administration & dosage, pharmacokinetics)
• Rats
• Rats, Wistar
• Serum Albumin, Bovine (administration & dosage, pharmacokinetics)
• Tissue Distribution