Bioavailability limitations

Nalidixic acid is another example of BCS class II drug, with oral bioavailability limited by poor solubility and slow dissolution (40). Compared to drug powder alone, the solid dispersion of nalidixic acid with P-cyclodextrin or PYP or sodium starch glycolate had much faster dissolution. X-ray diffraction studies revealed the formation of amorphous areas and less degree of crystallinity in the solid dispersion of nalidixic acid with excipients. 

Can be done on-site, in-place Bioavailability limitation other inorganics Physicochemical parameters... 

Neuraminidase is an essential viral glycoprotein for virus replication and release. The neuraminidase inhibitors zanamivir and oseltamivir have recently been approved for the treatment of acute uncomplicated influenza infection. When a 5-day course of therapy is initiated within 36-48 hours after the onset of symptoms, use of either agent shortens the severity and duration of illness and may decrease the incidence of respiratory complications in children and adults. Unlike amantadine and rimantidine, zanamivir and oseltamivir have activity against both influenza A and influenza B. Zanamivir is administered via oral inhaler. The compound displays poor oral bioavailability, limited plasma protein binding, rapid renal clearance, and absence of significant metabolism. Nasal and throat discomfort may occur—as well as bronchospasm in patients with reactive airway disease. 

Huesemann, M. H., Hausmann, T. S. Fortman, T. J. (2003). Assessment of bioavailability limitations during slurry biodegradation of petroleum hydrocarbons in aged soils. Environmental Toxicology and Chemistry, 22, 2853—60. 

The approach often taken in candidate optimization is to try to isolate bioavailability problems for a member of a chemotype of interest with a combination of in vitro and in vivo experiments and then to try to devise rapid techniques to screen for the liability (Fig. 8.1). This approach relies on a good deal of up-front work to fully understand the bioavailability limitations and periodic checking of the property to ensure that the screen is providing reliable... 

Elektorowicz M, Ju L, Oleszkiewicz J. (1999). Bioavailability limitations related to the presence of clays. In Bioavailability of Organic Xenobiotics in the Environment—Practical Consequences for Environment (eds. Ph Baveye, JC Block, VV Goncharuk). Dordrecht, the Netherlands Kluwer Academic Publishers, pp. 349-376. 

Classification of P2 purinoceptors has been limited by a lack of potent, selective, and bioavailable antagonists. Nonetheless a rational scheme for P2 purinoceptor nomenclature divides P2 receptors into two superfamilies P2Y5 LGIC family having four subclasses and P2Y) a GPCR family having seven subclasses. A third receptor type, designated the P22) is a nonselective ion pore. 

Chan LM, Lowes S, Hirst BH (2004) The ABCs of drug transport in intestine and liver efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 21 25—51... 

Stauber JL, Davies CM (2000) Use and limitations of microbial bioassays for assessing copper bioavailability in the aquatic environment. Environ Rev 8 255-301... 

However, most natural peptides are composed of L-form a-amino acids and because of the ubiquitous prevalence of peptidases they have limited biostability, and consequently low bioavailability. Thus, a novel field of peptidomimetics has emerged in drug discovery, in attempts to design non-peptide compounds mimicking the pharmacophore and thus the activity of the original peptide. 

Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci USA 1997 94 2031-5. 

Specific carotenoid-protein complexes have been reported in plants and invertebrates (cyanobacteria, crustaceans, silkworms, etc.), while data on the existence of carotenoproteins in vertebrates are more limited. As alternatives for their water solubilization, carotenoids could use small cytosolic carrier vesicles." Carotenoids can also be present in very fine physical dispersions (or crystalline aggregates) in aqueous media of oranges, tomatoes, and carrots. Thus these physicochemical characteristics of carotenoids as well as those of other pigments are important issues for the understanding of their bioavailability. 

For human studies, the choice of stable isotopes is limited because radioisotopes are associated with ionization radiation and thus with some potential harmful effects for humans. Studying the bioavailability of compounds labeled with stable isotopes requires complex techniques such as gas chromatography coupled with mass spectrometry (GC-MS), liquid chromatography coupled with MS (LC-MS), and atmo-... 

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. 

The extent to which bioavailability is a limiting factor and may be circumvented by addition of surfactants remains incompletely resolved. 

The prognosis for bioremediation of residues containing polychlorinated anilines and their impurities is rather discouraging. Important factors include (a) limited biodegradability, (b) restricted bioavailability, and (c) the possible formation of oligomeric coupling products. 

Additional hypotheses for their mechanism of action have more recently been proposed. It is well known that proanthocyanidins are able to complex metals through their ortho-diphenol groups. This property is often viewed as imparting negative traits (e.g., reduction of the bioavailability of essential mineral micronutrients, especially iron and zinc) [87]. Since iron depletion causes severe limitation to microbial growth, their ability to bind iron has been suggested as one of the possible mechanisms explaining the antimicrobial activity of proanthocyanidins [88] (Table 1). 

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