Screening methods bioavailability

Winfield LE, Development of a Plant-Based, Short-Term (<12 days) Screening Method for Determination of Hexahydro-1, 3, 5-trinitro-l, 3, 5-triazine (RDX) Bioavailability, Bioconcentration, and Phytotoxicity to Selected Terrestrial Plants from Soil Matrices, Ph.D. dissertation, University of Mississippi, University, MS, 2001. 

Bioavailability is an important parameter in drug screening cascades. It gives a good indication of the efficiency of the delivery of the compound to the systemic circulation by the chosen route. It can only be measured in vivo but, as will be described below, it can be predicted for man using a number of methods. 

The two patents described above were particularly important in the initiation of the developments of biodesulfurization catalysts. The bioreactor arrays required for operation and growth method constituted key elements in the following developments of the area, which would condition viability and successful path to industrialization. A sulfur bioavailability assay was incorporated into the screen for monitoring the sulfur uptake by the microorganisms, and the concept formed a claim in the patents [67,91], The objective... 

Given the overwhelming influence of the physical properties of skin in determining bioavailabilities via the dermal route, assessment of dermal penetration is one area in metabolism and toxicology where in vitro methods can be effectively used to predict in vivo results and to screen chemicals. Apparatus and equipment exist that one can use to maintain sections of skin (obtained from euthanized animals or from human cadavers or surgical discard) for such experiments (Holland et al., 1984). These apparatus are set up to maintain the metabolic integrity of the skin sample between two reservoirs the one on the stratum comeum side, called the application reservoir and the one on the subcutaneous side, called the receptor reservoir. One simply places radiolabeled test material in the application reservoir and collects samples from the receptor fluid at various time points. 

LC/MS/MS techniques with selective and sensitive detection methods make it possible to quantitatively analyze samples from Caco-2 cell and PAMPA buffer matrices. A high-throughput permeability screen with robust LC/MS technology can quickly generate information about structure-permeability relationships that are extremely valuable in the lead optimization phase for the selection of pre-clinical candidates with favorable oral bioavailability properties. 

---