Relative bioavailability factor

Passage to and targeting of a specific organ, such as the liver. The difference between uptake and intake is expressed by the so-called relative bioavailability factor (Oomen et al. 2006). 

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 authors also studied the influence of the chain length of alkylmaltosides on the nasal absorption of enoxaparin. The results indicated that increases in the concentration of alkylmaltosides increased the AUC for plasma anti-factor Xa it was found that the absolute and relative bioavailabilities of enoxaparin increased by twofold with an increase in alkyl chain length from 8 to 14 carbons. Of all the alkylmaltosides, TDM was found to be the most potent absorption enhancer [85], Furthermore, we have also shown the efficacy of cyclodextrins in enhancing absorption following the nasal delivery of LMWHs. Three different cyclodextrins were employed P-cyclodextrins (P-CD), hydroxypropyl p-CD (FIPP-CD), and dimethyl P-CD (DM(5-CD). P-CD showed therapeutic levels of anti-factor Xa only at 2.5 and 5% p-CD, but there was no significant difference between the two concentrations, which was attributed to their solubility limit. In the case of HPP-CD, neither 1.25 nor 2.5% produced an appreciable increase in anti-factor Xa levels ... 

Soil properties (edaphic factors) are important in determining bioavailability and include nutrient status, organic-matter content, soil structure, temperature, moisture and pH (Weber et al. 1993). Ageing is another important edaphic factor, because it appears that the amount of extractable contaminant decreases over time. For example, 8-14% of 14C-labelled 1,3,6,8-TCDD was found to become unextractable in soil after about a year in one study (Muir et al. 1985). It seems that a contaminant will diffuse into kinetically remote compartments of soil over time. It is possible, therefore, to distinguish three contaminant fractions a labile, relatively bioavailable fraction a recalcitrant, relatively firmly bound but still extractable fraction and a non-extractable, irreversibly bound fraction (Jones et al. 

Phase II studies, especially Phase Ilb studies, often require more-sophisticated formulations than those used in dose tolerance studies. However, it may be unwise to commit to a particular formulation strategy until after the clinical dose range is known. Therefore, formulations used in Phase II may not be as pharmaceutically elegant as marketed formulations. However, because bioavailability depends on formulation factors as well as intrinsic properties of the drug, bioavailability studies are conducted early in drug development to guide formulation development, establish the absolute or relative bioavailability of formulations used in clinical safety and efficacy studies, and determine the effect of food on bioavailability. 

Pb in diet on a daily or other time scale entail much larger amounts in terms of relative mass. For example, adults typically will consume only small amounts of lead in dusts and soils, 25—150 mg for various age bands, while ingesting food at a daily rate of 1 kg or more. Consequently, total daily intake of 100 mg of dust having a concentration of 1,000 ppm Pb yields the same Pb intake as 0.1 ppm Pb in 1.0 kg of diet. Other factors differentiating diet Pb from Pb in other media can potentially include a higher relative bioavailability of food Pb once ingested. 

The list of elements and their species listed above is not exhaustive. It is limited to the relatively simple compounds that have been determined by an important number of laboratories specializing in speciation analysis. Considering the economic importance of the results, time has come to invest in adequate CRMs. There is a steadily increasing interest in trace element species in food and in the gastrointestinal tract where the chemical form is the determinant factor for their bioavailability (Crews 1998). In clinical chemistry the relevance of trace elements will only be fully elucidated when the species and transformation of species in the living system have been measured (ComeUs 1996 Cornelis et al. 1998). Ultimately there will be a need for adequate RMs certified for the trace element species bound to large molecules, such as proteins. 

GIT, is considered to be lost from the absorption site, as is metabolic clearance and sequestration in various cell types and membranes (72,14). It is clear from Scheme I that the relative rates of the various processes will define the bioavailable fraction of the dose and understanding those factors which control pulmonary absorption kinetics is obviously the key to enhancing bioavailability via the lung. In a recent book (75) the molecular dependence of lung binding and metabolism was considered alongside the parallel processes of absorption, clearance and dissolution in the lung (14). Some key features of this work will be repeated as it relates to the systemic delivery of polypeptides. 

The bioavailability of drugs from tablets can be markedly influenced by the rate and efficiency of the initial disintegration and dissolution process. Unfortunately, one is faced with a compromise situation — a structure that has both a durable structure prior to administration and the ability to readily break down when placed in the in vivo environment. One of the major factors affecting both these properties is the structure of the tablet, in particular its density (or porosity) and the pore structure. Study of the significance of such measurements and interpretation of the results is a relatively recent field of interest. 

Comparison of the relative sediment toxicity of different SPs can be difficult as there are a variety of different test methods and endpoints evaluated, in addition to other confounding factors relating to sediment quality. Amweg et al. [28] determined the toxicity of six SPs to //. azteca in 10-day studies at 23 °C in natural sediments containing 1-6% OC. Toxicity data were reported as bulk sediment concentrations and normalized to the organic carbon content (Table 5). The results indicated that normalization removed some, but not all, of the variability between sediments. Other factors such as sediment texture may also affect bioavailability and hence apparent toxicity in sediment studies. 

Lyytikainen, M. Hirva, R Minkkinen, R Hamalainen, H. Rantalainen, A.-L. Mikkelson, P Paa-sivirta, J. Kukkonen, J.V.K. 2003a, Bioavailability of sediment-associated PCDD/Fs and PCDEs Relative importance of contaminant and sediment characteristics and biological factors. Environ. Sci. Technol. 37 3926-3934. 

---