Bioavailability assessment methods

The use of GC was first included in the United States Pharmacopoeia (USP) in the sixteenth edition in 1960, and became an official method of the British Pharmacopoeia (BP) in 1968. GC has found widespread use in pharmaceutical analysis by virtue of its applications to purity and control analysis of raw materials, content and quality assessment of dosage forms (including product stability), and in the quantitative measurement of drugs in biological fluids. The latter application is important for therapeutic drug monitoring, pharmacokinetic studies, and bioavailability assessments. In fact, in a survey on GC use, ° a major application of this technique was in the field of pharmaceuticals. 

There are also other BE-type assessments. Interaction studies assess the influence on bioavailability by other individual factors, such as food, alcohol, or other drugs. Such studies are usually single-sequence crossover, but the assessment method remains the same—whether confidence intervals of AUC and Cmax ratios fall within (0.80, 1.25). The same can be said of PK similarity assessments between subject populations, for example, healthy volunteers versus patients. The assessment method is the same as that used for BE, but important differences remain. In typical BE studies, subjects are densely sampled so that individual PK parameters, AUC and Cmax, can be determined with precision. PK similarity assessments are concerned with the differences in different populations, instead of formulations. The assessments are usually based on multiple (parallel) studies, as crossover studies are not possible, and sequence and period effects are not considered. Assessments involve obtaining estimates of average PK parameters in the populations and the 90% confidence intervals for the ratios of the average PK parameters. 

In this module, an emphasis is placed on the different methods that have been used for assessing the bioavailability of food pigments such as carotenoids. Different in vivo and in vitro approaches can be used to estimate pigment bioavailability from foods in humans. 

In order to exhibit provitamin A activity, the carotenoid molecule must have at least one unsubstituted p-ionone ring and the correct number and position of methyl groups in the polyene chain. Compared to aU-trans P-carotene (100% provitamin A activity), a-carotene, P-cryptoxanthin, and y-carotene show 30 to 50% activity and cis isomers of P-carotene less than 10%. Vitamin A equivalence values of carotenoids from foods have been recently revised to higher ratio numbers (see Table 3.2.2) due to poorer bioavailability of provitamin A carotenoids from foods than previously thought when assessed with more recent and appropriate methods. 

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. 

In such cases, the Nogami method can be applied to the early points curve (Fig. 6) and the solubility, S, of the polymorph can be assessed. One of the important aspects of metastable polymorphs in pharmacy is exactly their higher solubility, since the dissolution rate will also be higher [Eq. (7)]. Hence the bioavailability will be increased where this is dissolution rate limited [21]. 

Absorption and clearance are two of the fundamental parameters that determine oral bioavailability. There are many in vitro methods to assess the absorption and metabolic potential of a given molecule, and it can be argued that a combination of these data should produce a model capable of predicting oral bioavailability. Such a model, based on a graphical approach has recently been published [26]. 

Given the overwhelming influence of the physical properties of skin in determining bioavailabilities via the dermal route, assessment of dermal penetration is one area in metabolism and toxicology where in vitro methods can be effectively used to predict in vivo results and to screen chemicals. Apparatus and equipment exist that one can use to maintain sections of skin (obtained from euthanized animals or from human cadavers or surgical discard) for such experiments (Holland et al., 1984). These apparatus are set up to maintain the metabolic integrity of the skin sample between two reservoirs the one on the stratum comeum side, called the application reservoir and the one on the subcutaneous side, called the receptor reservoir. One simply places radiolabeled test material in the application reservoir and collects samples from the receptor fluid at various time points. 

The aim of this chapter is to highlight recent advances in fractionation techniques for grape seed PAs, using as examples methods we are using for large-scale fractionation into monomers, oligomers, and polymers for assessment of bioactivity and bioavailability in animal model studies of Alzheimer s disease. Our methods represent modifications/combinations of previously described approaches. We first discuss the available methods and modifications and then present a case study for the fractionation of MegaNatural-AZ GSE. 

One answer to this dilemma is to use computational methods to identify the most interesting and informative compounds to pursue. Several workers have devised rules to identify undesirable or desirable compounds (3-12). These applications generally rely upon hard rules or structural criteria applied with limited focus to define interesting compounds. For example, the rule-of-five utilizes a score of 0-4 and is meant to assess bioavailability issues alone. Triage methods eliminate compounds that violate one or more of a variety of rules, which results in a limited set of compounds passing all filters. This is in some... 

Whole-body isotope retention experiments were performed (via the method described above in the Smith experiment and with confirmed corrections for isotope decay rates), using extrinsically labeled ferric chloride hexahydrate and Ca from CCM (i.e., [ FeJFeCla and [" Ca] CaCl2) to determine the bioavailability of these minerals at an Fe Ca ratio of 1 167 mol/mol. CCM solubility was also assessed via a filtration method. 

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