Cyprotex adds PAMPA service for drug discovery

By Wai Lang Chu

- Last updated on GMT

Related tags: Pharmacokinetics

ADME/toxicity service providers, Cyprotex, launch a new service to
help drug discovery groups assess new oral drug candidates. The
service will equip researchers with new pharmacokinetic insights as
early as possible, aiming to improve on similar methods currently
available.

The service, known as prioritises compounds based on their potential to cross the gut wall and it is based on assessing permeability properties. It utilises mass spectrometry (LC-MS/MS), currently considered the most effective method for the task

This is in contrast to traditionally employed absorbance measurements, as the service, Cloe Screen PAMPA (Parallel Artificial Membrane Permeation Assay), uses LC-MS/MS) as an end-point to ensure greater data accuracy and sensitivity.

Armed with this data enables drug researchers to see how their compounds behave in the different pH environments that exist throughout the entire gastro-intestinal tract. This gives them a good idea of how much of their compounds might reach their target organs in order to be effective therapies.

"The Cloe Screen PAMPA offers our partners a fast turnaround assay that displays reproducibility,"​ said Dr Darwin Cheney, Cyprotex​'s Chief Scientific Officer.

"We have also demonstrated that the assay shows several fold improvement in sensitivity over currently available PAMPA assays."

The PAMPA assay is one of only two widely utilised methods for modelling intestinal permeability that does not involve biological preparations.

As drug bioavailability is influenced by factors including absorption and metabolism, PAMPA assays use membranes coated with a mixture of phospholipids in dodecaine to assess the effectiveness of passive transport across the membrane barrier.

In incorporating predictive ADME assays in progressively earlier stages of drug discovery can help in rejecting molecules that lack necessary pharmacological properties.

PAMPA has the advantage of being effective under a wide variety of experimental conditions. This includes the use of vastly different pH's, cosolvents, excipients, and chemical additives.

An additional advantage of utilising artificial membranes is its potential for higher throughput. The 96-well format PAMPA assays can usually be read by most modern plate readers in under a minute, rather than the hours it would take to analyse each sample individually by LC/MS.

Disadvantages include the lack of enzymes, influx and efflux transporters, and modeling of paracellular pathways. These disadvantages can lead to misleading results and should always be considered when relying solelyon artificial membranes to predict oral bioavailability.

Related topics: Preclinical Research

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