Measurements bioavailability

Data presented in this review also address a bio availability issue, in vivo antigen delivery. Bioavailability measures how much of the drug molecule arrives at its site of action compared with how much is in the formulation delivered to the... 

Pharmacokinetic studies on glucosamine sulfate in man showed that uptake into plasma proteins peaked at 8-10 hr, and the half-life was about 70 hr after administration. However, oral administration yielded only 26% of the bioavailability (measured from plasma levels after any first pass metabolism) of the other two routes of administration via injection, but the glucosamine sulfate was detected in bones and cartilage afterwards. ... 

An even more refined PSA-based filter that also takes into account molecular flexibility is based on the analysis of oral bioavailability measurements in rats for over 1,100 drug candidates. The following two criteria were suggested for achieving bioavailability in rats above 20 0% ... 

Figure 35.22 Compound optimization. Four compounds are evaluated for characteristics including the IC50 (the compound concentration required to reduce HIV replication to 50% of its maximal value), log P, and c ax (the maximal concentration of compound present) measured in the serum of dogs. The compound shown at the bottom has the weakest inhibitory power (measured by IC50) but by far the best bioavailability (measured by Cmax)- f compound was selected for further development, leading to the drug indinavir (Crixivan).

Analysis of the mineralization results is complicated by the competing effects of mass transfer, biodegradation, sequestration, and transformation, all of which are specific to our experimental conditions. This makes classification and generalization of the results difficult, at best. Previous attempts to generalize bioavailability measures have focused on developing either numerical models or correlations based on soil type. These models often focus on either biodegradation or mass-transfer, and make simplifying assumptions about the other phenomenon. 

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 term bioavailability has various definitions. Previously, the authors of this chapter have defined bioavailability as the proportion of a nutrient (or other food component) that is digested, absorbed and utilised in normal metabolism - with the practical measurement of bioavailability usually relying upon estimates of amounts absorbed (Southon and Faulks, 2001). Biological activity, or bioactivity , has been viewed and described as a separate stage which follows on from bioavailability in the journey of a compound from food to function. However, here we present a new definition of bioavailability that recognises the functional consequences of absorption. 

The absorption and transport processes of many of the phytochemicals present in food are complex and not fully understood, and prediction of their bioavailability is problematic. This is particularly true of the lipid-soluble phytochemicals. In this chapter the measurement of carotenoid bioavailability will be discussed. The carotenoids serve as an excellent example of where too little understanding of food structure, the complexity of their behaviour in foods and human tissues, and the nature and cause of widely different individual response to similar intakes, can lead to misinterpretation of study results and confusion in our understanding of the relevance of these (and other) compounds to human health. 

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

A major drawback of this study was that we measured lipid peroxidation ex vivo, but not in vivo using the latest and most promising methods such as F2 isoprostanes (Roberts and Morrow, 2000). However, we are planning to do that soon, so hopefully future studies will bring us more detailed information about the effects of phloem on lipid peroxidation. In conclusion, our study showed that lignans are bioavailable from the wood matrix, that long-term consumption of phloem is safe and that ingestion of phloem can inhibit lipid peroxidation in humans. 

In the total plasma response approach, the bioavailability of a compound is determined by measuring its plasma concentration at different times (up to weeks) after single or long-term ingestion of the compound from supplements or food sources. Generally, a plasma concentration-versus-time plot is generated, from which is determined the area-under-curve (AUC) value used as an indicator of the absorption of the componnd. Here, the term relative bioavailability is more appropriate since AUC valnes of two or more treatments are usually compared. This is in contrast to absolnte bioavailability for which the AUC value of the orally administered componnd is compared to that obtained with intravenous administration taken as a reference (100% absorption). 

Avdeef, A. High-throughput Measurement of Membrane Permeability. In Drug Bioavailability (Methods and Principles in Medicinal Chemistry), Van de Waterbeemd, H Lennemas, H Armrsson, P. (eds.), Wiley-VCH, Weinheim, 2003, pp. 46-71. 

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