Pharmacokinetics and Tissue Distribution of DVDMS-2 in Tumor-bearing Mice

Photochem Photobiol. 2020 Jan;96(1):148-155. doi: 10.1111/php.13171. Epub 2019 Nov 4.

Abstract

DVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg-1 ) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay. The data obtained were processed with WinNonlin pharmacokinetic software. The fluorescence assay established for DVDMS-2 quantification was a rapid, reproducible, sensitive and specific method with good linearity. The pharmacokinetics of DVDMS-2 in tumor-bearing mice conformed to a two-compartment model. DVDMS-2 accumulated in tumor tissue to a greater extent than adjacent tissues (skin, muscle) and sustained a relatively high-level concentration 12 to 24 h following administration, which may be the optimal treatment time point. In conclusion, DVDMS-2 selectively accumulated in tumor tissue and was eliminated at a rapid rate in tumor-bearing mice, suggesting that DVDMS-2 may have few side effects, including skin phototoxicity. The present study established the pharmacokinetic characteristics of DVDMS-2, which may be beneficial in future clinical study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / drug therapy*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacokinetics*
  • Photosensitizing Agents / therapeutic use
  • Porphyrins / administration & dosage
  • Porphyrins / pharmacokinetics*
  • Porphyrins / therapeutic use
  • Spectrometry, Fluorescence
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Photosensitizing Agents
  • Porphyrins
  • sinoporphyrin sodium