Planta Med 2012; 78 - PJ55
DOI: 10.1055/s-0032-1321215

Determination of in vitro CACO-2 permeability and oral pharmacokinetic profile of Platycodin D in rats

IJ Ha 1, YS Kim 1
  • 1College of Pharmacy/Natural Products Research Institute, Seoul National University, Seoul, Korea

Platycodin D (PD) was regarded to be major active components of the roots of Platycodon grandiflorum for the various bioactivities. However, there have been relatively few studies determining ADME and pharmacokinetic properties.

High-performance liquid chromatography with evaporative light scattering detector method was developed and validated to determine the permeability of PD, deapio-platycodin D (De-PD) and platycoside F (PF). The Papp values of PD, De-PD, and PF (Concentration, 100µM) in the absorptive direction were 29.1 34.9, and 25.2at a level of 10-6 cm/s, respectively. The efflux ratio were between 0.45–0.53. The three compounds have high permeability in the Caco-2 cell monolayer without the effect of efflux transport. A simple, rapid and sensitive method for the determination of platycodin D in rat plasma was developed using liquid chromatography electrospray ionization mass spectrometry. This method was further applied to determine the pharmacokinetic study of PD after a single oral administration in rats. Quantification of rat plasma samples pretreated by protein precipitation was performed by LC-ESI/MS in negative selective ion monitoring mode. After a single oral dose of 10mg/kg, the peak plasma concentration (C max) of platycodin D was 28.9±9.03. The time to reach C max (T max) was 60 (45–240)min. The terminal elimination half-life (T 1/2) was about 201±80.6min.