First Pass Metabolism Model

First Pass Metabolism Model2023-06-30T10:15:08-05:00


  • For most applications, it is ideal to administer the therapeutic as an oral pill, it is cost effective to deliver and overall patients seem to prefer this method.
  • However, many therapeutics cannot be administered orally due to how the body absorbs and metabolizes them which can result in too low of a bioavailability.
  • MatTek and Visikol have developed an in vitro model system specifically for this purpose.
  • The model combines the MatTek EpiIntestinal™ model with the Visikol HUREL® micro liver model to create a two-organ system for quantifying first pass metabolism.
  • This model combines two of the most well validated in vitro model systems in the entire space together to form a unique organ system on a plate which provides researchers with a tool to assess the optimal route for therapeutic administration.
  • Visikol is now offering this First Pass Metabolism Model to clients as part of its comprehensive contract research services to assess the metabolism of potential therapeutics.

Cell Culture Inserts

MatTek Multi-Well Plates

The First Pass Metabolism Model uses MatTek 96-well glass bottom dishes. These dishes have a gas plasma treatment and collagen coating surface modification on the bottom plate.

Experimental Methods

Culture System
  • Human Intestine (control): MatTek 96w
  • Human Intestine/Liver (first pass metabolism model): HUREL micro liver
  • Used MatTek 96 transwell plate for the Intestine/Liver cell culture
    -Bottom plate: surface treatment and collagen Type I coating
  • Dosing volume:
    -Upper compartment: 100 ul dosing compounds
    -Lower compartment: 300 ul dosing media (HUREL)
  • Time points: t=24hr
  • Replicate: n=3
  • Drug Metabolism
  • Drug Clearance (5 uM)
  • Drug Permeability (10 uM)
  • Drug Inflammation
  • TEER Measurement
  • LC-MS/MS

Drug Metabolism: Cytochrome P450 enzymes

Significantly higher metabolite formation in the First-Pass Metabolism Model as shown by CYP3A4, CYP2D6, CYP1A2 and CYP2C9 activity as well as Phase II metabolism.

Drug Clearance/Bioavailability

Higher clearance (lower bioavailability) of drugs in first pass metabolism model as demonstrated by Bupropion, Verapamil, Diazepam, Repaglidine, Dextromethorphan and Troglitazone.

Drug Permeability

Highly Permeable Compounds:

  • Quinidine
  • Warfarin

Poorly Permeable Compounds:

  • Atenolol
  • Ranitidine
  • Talinolol

TEER (transendothelial electrical resistance) Measurement

Intestine tissue on the multi-well plate membrane maintains good integrity and permeability.