Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats

Molecules. 2021 Jul 14;26(14):4276. doi: 10.3390/molecules26144276.

Abstract

Forchlorfenuron (CPPU) is a plant growth regulator extensively used in agriculture. However, studies on CPPU pharmacokinetics are lacking. We established and validated a rapid, sensitive, and accurate liquid chromatography-mass spectrometry method for CPPU detection in rat plasma. CPPU pharmacokinetics was evaluated in adult and juvenile rats orally treated with 10, 30, and 90 mg/kg of the compound. The area under the plasma drug concentration-time curve from 0 to 24 h (AUC), at the final time point sampled (AUC0-t), and the maximum drug concentration of CPPU increased in a dose-dependent manner. The pharmacokinetic parameters AUC0-t and absolute bioavailability were higher in the juvenile rats than in adult rats. The mean residence time and AUC0-t of juvenile rats in the gavage groups, except for the 10 mg/kg dose, were significantly higher in comparison to those observed for adult rats (p < 0.001). The plasma clearance of CPPU in juvenile rats was slightly lower than that in the adult rats. Taken together, juvenile rats were more sensitive to CPPU than adult rats, which indicates potential safety risks of CPPU in minors.

Keywords: forchlorfenuron; juvenile rat; liquid chromatography-mass spectrometry; pharmacokinetics.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Male
  • Phenylurea Compounds / pharmacokinetics*
  • Plasma / metabolism
  • Pyridines / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods

Substances

  • Phenylurea Compounds
  • Pyridines
  • N-(2-chloro-4-pyridyl)-N'-phenylurea