Pharmacokinetic studies in RjHan:SD rats

Pharmacokinetic, in vivo screening
Figure 1: Concentration of a small molecule in blood after p.o. application determined by LC-MS

Species

Rat

Field of application:

Catheter-implanted rats are used. One catheter is placed in the left carotid artery and one in the right common jugular vein. Vascular accesses are used for application of small molecules and for subsequent blood collection. Advantage of using rats is the determination of full pharmacokinetic profiles from single animals. Compound concentration is determined by LC-MS.

The model can be used for the following fields of application:

  • ADME screening
  • Pharmacokinetics
  • Proof of concept

Endpoints/Outcome parameter

  • Different routes of application (i.v., p.o., s.c., i.p.)
  • Pharmacokinetic Parameters:
    • cmax [ng/ml]
    • tmax [h]
    • AUC [(ng*h)/ml]
    • t1/2 [h]
    • F [%]

Readout parameter

  • Blood collection
  • Compound concentration determined by LC-MS

Quality management and validation

  • Individual method development and validation for LC-MS
  • Pharma-like documentation, e.g. by electronic laboratory notebook and compound management system
  • Internal quality management
  • LC-MS can be performed under GLP conditions

Weblink(s)

https://www.izi.fraunhofer.de/de/departments/halle-location/department-of-drug-design-and-target-validation/molecular-biotechnology.html#tabpanel-3

References

  • Feng, J., Fitz, Y., Li, Y., Fernandez, M., Cortes Puch, I., Wang, D., et al. Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model. J. Vis. Exp. (95), e51881, doi:10.3791/51881 (2015).