Bioavailability development

It is also important to develop an understanding of the movement of chemicals through the environment by investigating their fate and behaviour. Based on a chemical s inherent physicochemical properties, it is possible to predict with some degree of certainty which environmental compartment it is likely to reside in and to what extent it is likely to be bioavailable and accumulate through the food chain. 

Recently, leaders in the pharmaceutical industry have developed a list of desired properties for a fourth generation of SERMs (Table 2). In general, future SERMs must oppose endogenous hormone action in the breast and reproductive system while displaying full estrogenic effects in the cardiovasculature, bone and central nervous systems. Additional criteria are that fourth generation compounds possess superior bioavailability compared with existing SERMs and have... 

Bioavailability studies play a critical role in the evaluation of product formulations throughout the entire development process. 

As is the case with assessments of the toxicity of dissolved trace metals, the development of sediment quality criteria (SQC) must be based on the fraction of sediment-associated metal that is bioavailable. Bulk sediments consist of a variety of phases including sediment solids in the silt and clay size fractions, and sediment pore water. Swartz et al. (1985) demonstrated that the bioavailable fraction of cadmium in sediments is correlated with interstitial water cadmium concentrations. More recent work (e.g., Di Toro et al, 1990 Allen et al., 1993 Hansen et al, 1996 Ankley et ai, 1996, and references therein) has demonstrated that the interstitial water concentrations of a suite of trace metals is regulated by an extractable fraction of iron sulfides. 

Polymeric microparticles have been studied and developed for several years. Their contribution in the pharmacy field is of utmost importance in order to improve the efficiency of oral delivery of drugs. As drug carriers, polymer-based microparticles may avoid the early degradation of active molecules in undesirable sites of the gastrointestinal tract, mask unpleasant taste of drugs, reduce doses and side effects and improve bioavailability. Also, they allow the production of site-specific drug targeting, which consists of a suitable approach for the delivery of active molecules into desired tissues or cells in order to increase their efficiency. 

Traditionally, in pursuit of their structure-activity relationships, medicinal chemists had focused almost exclusively on finding compounds with greater and greater potency. However, these SARs often ended up with compounds that were unsuitable for development as pharmaceutical products. These compounds would be too insoluble in water, or were not orally bioavailable, or were eliminated too quickly or too slowly from mammalian bodies. Pharmacologists and pharmaceutical development scientists for years had tried to preach the need for medicinal chemists to also think about other factors that determined whether a compound could be a medicine. Table 1.1 lists a number of factors that determine whether a potent compound has what it takes to become a drug. Experimentally, it was difficult to quantitate these other factors. Often, the necessary manpower resources would not be allocated to a compound until it had already been selected for project team status. 

Development candidates must be measured against multiple performance criteria, including such aspects as potency, safety, and novelty. Conflict may be experienced between the criteria, in which improved performance in one criterion can only be achieved at the expense of detriment to another. In this situation—as is often the case for activity against bioavailability—a trade-off is said to exist between the objectives. A trade-off between potency and safety may also be present. 

The aim of our project was to study phloem as a source of fiber and polyphenols, and to develop a method to improve its taste without losing the potentially bioactive polyphenols. In addition, we wanted to investigate the bioavailability, cholesterolemic and antioxidative effects and safety of phloem and its phytonutrients in humans in a randomised double-blind trial. 

Based on the limitations of using human subjects, simple alternative in vitro models were developed to investigate mechanisms involved in the intestinal absorption process of a compound of interest and to screen the relative bioavailability of a compound from various food matrices. However, the data generated from in vitro approaches must be taken with caution because they are obtained under relatively simplified and static conditions compared to dynamic physiological in vivo conditions. Indeed, the overall bioavailability of a compound is the result of several complex steps that are influenced by many factors including factors present in the gastrointestinal lumen and intestinal cells as described later. Nevertheless, these in vitro approaches are useful tools for guiding further smdies in humans. 

Garrett, D.A., Failla, M.L., and Samara, R.J., Development of an in vitro digestion method to assess carotenoid bioavailability from meals, J. Agric. Food Chem., 47, 4301, 1999. 

As for PAHs, attempts have been made to increase bioavailability by use of surfactants, and a complex picture has again developed (Fava and Di Gioia 1998). Triton-100 exerted both positive and negative effects in soil slurries even though it was not metabolized by the soil microflora, it adversely affected the degradation of chlorobenzoate intermediates, whereas in fixed-bed reactors, depletion of PCBs was enhanced. 

Phytic acid (inisitol hexakisphosphate) is the main storage form of phosphorus in plants. The phosphorus is not bioavailable to non-ruminants as they lack the enzymes to break it down. Novozyme has developed a commercial enzyme, phytase, that can be added to animal feed to release the phosphorus. No inorganic phosphorus needs to be added. This shift in the source of phosphorous has a large impact on the environmental footprint of pig farming. 

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