Bioavailability reduction

The amount of bioavailable reductant (organic and inorganic substances) available for microbial utilization... 

It may be said that recent developments in cyclodextrin (CD) applications in drug formulations are concerned with stabilization enhancement of solubility novel preparative methods of inclusion complexes enhancement of bioavailability reduction of topical or hemolytic side effects on administration absorption enhancement in transdermal application. 

Fine particle technology has broad applications in medicine for both therapeutics and diagnostics. The most common use of finely dispersed systems occurs in oral products that contain poorly water-soluble active agents. Fine (micro or nano) particles have increased surface area per unit dose relative to coarse active agent particles. As a result, the fine particles have much more favorable dissolution kinetics in-vivo. This can lead to increases in oral bioavailability, reductions in food-effect-associated variability, and more i id absorption and onset of therapeutic action. Topical delivery of active agent particles can also be enhanced when they are formulated as finely dispersed systems. 

Pharmacokinetic studies demonstrated good oral bioavailability of maraviroc and a terminal half-life of 16-23 h following multiple dosing (Abel et al. 2003 Walker et al. 2005). Single doses of up to 900 mg and multiple doses of up to 300 mg BID for 28 days were well tolerated (Abel et al. 2003 Russell et al. 2003 Walker et al. 2005). In Phase 2a studies, treatment-naive HIV-1 patients with R5 virus who received maraviroc monotherapy at doses ranging from 25 mg QD to 300 mg BID for 10 days experienced a median viral load reduction of 1.64 log jg copies/mL and... 

Cyanidin is the most common anthocyanin in foods. In addition, anthocyanins are stabilized by the formation of complexes with other flavonoids (co-pigmentation). In the United States, the daily anthocyanin consumption is estimated at about 200 mg. Several promising studies have reported that consumption of anthocyanin-rich foods is associated with reductions of the risks of cancers - and atherosclerosis and with preventive effects against age-related neuronal and behavioral declines. These beneficial effects of anthocyanins might be related to their reported biological actions such as modulators of immune response and as antioxidants. Knowledge of anthocyanin bioavailability and metabolism is thus essential to better understand their positive health effects. 

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). 

Investigation of the differences in crystal packing between (431) and (426) from comparison of their respective X-ray structures, revealed that (431) was more tightly packed than (442), reflected in their respective melting points of 235 and 170 °C. It was postulated that the absence of in vivo activity for (431) may be explained by the resultant reduction in water solubility and dissolution rate compared with (426). The comparatively high calculated polar surface area of (431) (122.5A ) compared with (426) (89.3 A ) was also proposed as a factor influencing the marked difference in bioavailability between the two related compounds. Compound (426) (SLV-319) is currently being developed with Bristol-Myers Squibb for the potential treatment of obesity and other metabolic disorders. Phase I trials for obesity were started in April 2004. Earlier Phase I clinical trials for the treatment of schizophrenia and psychosis, which commenced in April 2002, appear to have been abandoned. 

The effect of particle size reduction on the bioavailability of nitrofurantoin was shown in Fig. 4. The microcrystalline form (< 10 pm) is more rapidly and completely absorbed from the tablet dosage form than is the macrocrystalline form (74-177 pm) from the capsule dosage form. This is not a completely satisfactory illustration of the effect of particle size on the rate and extent of availability, since other manufacturing variables have not been held constant. Nevertheless, it does suggest some correlation between particle size, dissolution rate, and rate of availability. 

Evaluating the use of composts for reduction of the bioavailability and phytoavailability of lead and other heavy metals in contaminated soils... 

Bolger PM, Carrington CD, Capar SG, et al. 1991. Reductions in dietary lead exposure in the United States. Chemical Speciation and Bioavailability 3(314) 31-36. 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

Soil pH affects the transformation of Cr between Cr(III) and Cr(VI) in soils. Since Cr(VI) has greater bioavailability and mobility in soils than Cr(III), which is strongly bound by soil solid matrix (Han and Banin, 1997). Cr(III) can be oxidized by soil manganese oxides into Cr(VI), while Cr(VI) can be reduced by organic matter, Fe(II) and microorganisms in soils. Reduction of Cr(VI) has been found to occur much slower in alkaline soils compared to acid soils (Cary et al., 1997). 

Potential obstacles for the large-scale application of phytoremediation technologies, however, include the time required for remediation, the pollutant levels tolerated by the plants used, the disposal of the contaminated plants, and the fact that only the bioavailable fraction of the contaminants will be treated. This means that phytoremediation does not achieve 100% removal or reduction of the contaminants From the ecological, toxicological, and medical (health) points of view, the... 

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