Drug absorption assessment is crucial in investigating ADME of novel pharmaceuticals. Creative Biolabs provides various custom-designed studies to better understand in vitro ADME.
Drug absorption is the movement of a drug into the bloodstream. Many factors influence this process, including a drug's physicochemical properties, formulation, and route of administration. Generally, for oral treatment, the drug needs to be introduced via the intestinal pathway to blood. For other routes, like intravenous therapy, intramuscular injection, and enteral nutrition, absorption is more straightforward to blood. No matter what kind of administration routes, drugs must be dissolved and absorbed for therapeutic effects. By adjusting factors that affect absorption, the pharmacokinetic (PK) profile of a drug can be changed.
A drug's permeability across biological membranes is a key factor that influences the absorption and distribution. This is because if a drug wants to reach to the systemic circulation, it needs to cross several semipermeable cell membranes firstly. Drugs may cross cell membranes by passive diffusion, facilitated passive diffusion, active transport, and pinocytosis. The drug's physicochemical properties (such as size and lipophilicity), as well as membrane-based efflux mechanisms, can lead to poor permeability.
Figure 1. Representation of the enterocyte showing the colocalization of CYP3A4 and P-gp (Paine et al. 2004)
Creative Biolabs offers several in vitro methods to access permeability of drugs and predict drugs' in vivo absorption. Our research platforms include:
Skin absorption is a route of administration for medication by which drugs can enter the body through the outer surface of the skin and treat skin-related disease. Assess skin absorption level is contributed to improving the effect of drugs and reducing skin irritation, corrosion, and sensitization. Creative Biolabs uses different methods to assess dermal absorption. We use split-thickness human or animal skin as models for static diffusion and flow-through diffusion for dermal penetration testing.
Parallel Artificial Membrane Permeability Assay (PAMPA)
Parallel artificial membrane permeability assay (PAMPA) is an in vitro model of passive diffusion and is used to determine the permeability of a drug. A lipid-infused artificial membrane is generated and acts as a supplement for cell-based assays. The test compound is added to the donor compartment and permeating an artificial hexadecane membrane to the acceptor compartment. The result is quantified by LC-MS/MS. This method only measures permeability by passive diffusion.
The Caco-2 cell line is derived from a human colon carcinoma and has many characteristics that resemble intestinal epithelial cells. Caco-2 permeability assay is a good way to investigate human intestinal permeability and drug efflux. Caco-2 permeability assay measures the rate of transporting of a compound across the Caco-2 cell and assesses transport in both directions. Creative Biolabs delivers a highly automated and cost-efficiency Caco-2 permeability assay to determine the permeability and absorption of a lead.
The Madin-Darby canine kidney (MDCK) cell is an epithelial cell line of canine kidney origin which has low expression of transporter proteins and low metabolic activity. Compared to Caco-2 cell, MDCK cell grows and differentiates more quickly. Therefore, it provides an attractive alternative to Caco-2 cells to assess the human intestine barrier. Creative Biolabs provides reliable MDCK and MDR1-MDCK permeability assay services to determine drug permeability.
Transporter Substrate Identification
Active transport is selective. It seems to be limited to the small amount of drugs whose structural are similar to endogenous substances (e.g., ions, vitamins, amino acids). Drug transporters expressed in intestine, liver, brain, and kidney and the transporters can be divided into efflux transporters and solute carriers (SLC). Creative Biolabs measures an efflux ratio through monolayer to determine whether a compound undergoes active transport. The efflux transporter inhibitor can identify whether active transport is mediated by efflux transporter.
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Reference
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