Bioavailability standard variables

Figure 5. Ca + bioavailability to mice. The animals were administered by gavage 200 ul of 0.1 mM (cross-hatched) and 1.0 mM CaCl2 (dotted) containing variable amounts of phytic acid as indicated on the abscissa. The mean and standard deviation of 4 to 9 determinations of Ca2+ absorption into the blood after 4 hours are shown on the ordinate. (Reproduced with permission from Ref. 26. Copyright 1984 J. Nutr., American Institute of Nutrition.)...

The strength of the bioassay approach is that it directly estimates the fraction of natural DOC that can be used by a natural microbial assemblage under defined conditions. However, there are numerous manipulations of water samples during bioassay incubations, and the effects of these manipulations on the measured parameters are not well known. For example, containment of water samples can rapidly alter microbial population structure. Nutrients, rather than carbon, can be limiting for microbial utilization of DOM. Moreover, there are no standard protocols for bioassay experiments. Different indicators of DOM utilization are measured by different investigators, and many of the measured parameters rely on conversion factors that are also quite variable. The extent of DOM utilization also depends upon the duration and temperature of the bioassay experiment. Despite these shortcomings, the bioassay experiment remains the best approach for estimating the bioavailability of DOM. 

The results are then expressed as the amount of drug recovered from the tape strips against time. Uptake and elimination phases are observed (Fig. 9) and bioavailability may be predicted from the area under the curve. There are several sources of variability in such studies, all of which must be considered in standard operating procedures. The major causes of concern in variability are ... 

It should also be borne in mind that a complex biological property such as bioavailability is influenced by many factors as discussed in this chapter. The result is the considerable interindividual variability of about 15% standard deviation in observed bioavailability. The consequence of this is that any modeling approach cannot be better than this (Figure 16.3). 

In these studies, standard bioavailability variables such as the extent of bioavailability determined from area under the curve (AUC), rate of bioavailability related to peak plasma drug levels (Cmax) and time to peak (fmax) are determined. A more detailed presentation of the assumptions and interpretations of bioavailability data is given in Chapter 7. The bioavailability after administration in more distal parts of the intestine, such as the terminal ileum and different parts of the colon, is compared with a reference administration either as an oral solution or as a regional delivery to the upper small intestine. This is exemplified in Figure 4.18, which shows the plasma drug concentrations of metoprolol after administration to jejunum, terminal ileum and colon ascendens or transversum. 

The standard bioavailability variables after a single-dose administration are the maximum plasma concentration (Cmax), the time to reach Cmax (fmax) and the area under the plasma concentration—time curve from time zero to infinity (AUC). 

Separate mass balance equations are written in the form of Section 10.6.2 for each of the two compartments. Variables and A2 represent the amount of drug in compartment 1 and compartment 2, respectively, and the total amount of drug in the body is given by the sum of Ai and A2. The rate of drug absorption is a function of a first-order absorption rate constant kj, the bioavailability (F), and the administered dose (D). Distribution between the compartments follows first-order kinetics as described previously. Elimination occurs only from compartment 1 in the standard model form, with the elimination rate equal to the amount of drug remaining in compartment... 

PbB has long been used as the standard index of dose in estimating dose-effect and dose-response relationships. Some would argue that it is perhaps less valid than certain other measurements which reflect in quantitative fashion the bioavailable fraction of PbB, much as erythrocyte cholinesterase inhibition reflects the toxic impact of exposure to organophosphate insecticides. Indeed, it has been reported that inhibition of erythrocyte membrane Na, K-ATPase activity is better correlated with lead toxicity than erythrocyte lead concentration (Raghavan ei al, 1981). This was attributed to the fact that the subjects had variable concentrations of a low molecular weight lead binding protein which influenced the bioavailable fraction of PbB. It is possible that EP reflects bioavailable lead in a similar fashion. 

The folate requirement is the minimum amount necessary to prevent deficiency. Dietary recommendations for populations, however, must allow a margin of safety to cover the needs of the vast majority of the population. As is the case with most nutrients, the margin of safety for folate requirement corresponds to two standard deviations above the mean requirement for a population and should therefore meet the needs of 97.5% of the population. Thus, international dietary recommendations contain allowances for individual variability, the bioavailability of folate from different foodstuffs, and periods of low intake and increased use. Current international folate recommendations for FAO/ WHO, USA/Canada, and the European Union are listed in Table 2. 

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