Pharmacokinetics of trifluralin in blood and heart tissue of mice

Chemotherapy. 2009;55(5):327-34. doi: 10.1159/000230696. Epub 2009 Jul 27.

Abstract

Background: Trifluralin displays anti-Trypanosoma cruzi activity and a potential therapeutic effect for the treatment of Chagas disease. We assessed peroral and intramuscular trifluralin pharmacokinetics in mouse blood and heart tissue.

Methods: A parallel experimental design was used. Healthy adult male CF1 albino mice (n = 108, 25-35 g bw) received a single peroral or intramuscular trifluralin dose (50 mg/kg in peanut oil). Blood and heart tissue samples were taken at set times after intramuscular and peroral trifluralin administration. Feces and tissue samples were taken 12 h after intramuscular trifluralin administration. Trifluralin concentrations in whole blood, feces and tissues were determined by HPLC.

Results: After intramuscular and peroral administration, maximum whole blood concentration (C(max)) was attained at 30 min and 2.0 h (t(max)) (28.2 +/- 0.7 and 7.8 +/- 0.033 microg/ml; p < 0.05). C(max) in heart tissue was attained at 1.0 and 2.0 h (0.6 +/- 0.004 and 0.2 +/- 0.002 microg/g; p < 0.05). Liver, perirenal and subcutaneous fat concentrations were 55.1, 66.3 and 59.7 ng/mg tissue protein. Peroral and intramuscular penetration ratios determined by comparing heart tissue areas under the curve were 6.3 and 4.0%, respectively.

Conclusion: Intramuscular trifluralin could be a new alternative for the treatment of Chagas disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Chagas Cardiomyopathy / drug therapy
  • Chagas Disease / drug therapy
  • Feces / chemistry
  • Humans
  • Liver / metabolism
  • Male
  • Mice
  • Myocardium / metabolism*
  • Trifluralin / blood
  • Trifluralin / chemistry
  • Trifluralin / pharmacokinetics*
  • Trypanocidal Agents / blood
  • Trypanocidal Agents / pharmacokinetics*

Substances

  • Trypanocidal Agents
  • Trifluralin