Bioavailability defined

Oral administration is the most popular route due to ease of ingestion, pain avoidance, versatility, (to accommodate various types of dmg candidates), and, most importantly, patient compliance [119]. In addition, solid oral delivery systems do not require sterile conditions and are, therefore, less expensive to manufacture. Orally delivered pharmacologically active compounds must have favorable absorption and clearance properties, and satisfactory metabolic stability to provide adequate systemic exposure to elicit a pharmacodynamic response. If the compounds possess reasonable physicochemical properties have low to intermediate clearance and reasonable absorption, adequate oral bioavailabdity may be achieved [120]. Indeed, oral bioavailability, defined as the rate and extent to which the active dmg is absorbed from a pharmaceutical form and becomes available at the site of dmg action [121], is influenced by several factors including solubility, permeability, intestinal and liver metabolism, rapid biliary and other efflux pump-mediated excretion, and conditions in the gastrointestinal milieu [122,123]. Thus, both absorption and elimination processes determine the oral bioavailability F of a given dmg. Accordingly, F can be estimated as... 

In addition to the three parameters, clearance (CL), bioavailability (F), and volume of distribution (V) discussed previously, a fourth parameter, half-life ( 1/2), is also crucial in therapeutics. The decreasing order of importance of these four parameters is clearance, bioavailability, half-life, and volume. Clearance defines the dosing rate, bioavailability defines dose adjustment, and half-life defines the dosing interval. Volume of distribution defines the loading dose. 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

The behavior of elements (toxicity, bioavailability, and distribution) in the environment depends strongly on their chemical forms and type of binding and cannot be reliably predicted on the basis of the total concentration. In order to assess the mobility and reactivity of heavy metal (HM) species in solid samples (soils and sediments), batch sequential extraction procedures are used. HM are fractionated into operationally defined forms under the action of selective leaching reagents. 

The systemically available fraction or bioavailability (F) can be defined by the fraction of the area after- oral and intravenous dosing, respectively. 

To maximize safety and therapeutic efficacy, potential drugs are required to be highly specific for their protein target and orally bioavailable. In addition, for a drug candidate to reach the market, it must be patentably novel. A computational approach therefore needs to find novel compounds with well-defined pharmacological properties from the vast space of possible organic compounds ( chemical space ). 

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 bioaccessibility of a compound can be defined as the result of complex processes occurring in the lumen of the gut to transfer the compound from a non-digested form into a potentially absorbable form. For carotenoids, these different processes include the disruption of the food matrix, the disruption of molecular linkage, the uptake in lipid droplets, and finally the formation and uptake in micelles. Thus, the bioaccessibility of carotenoids and other lipophilic pigments from foods can be characterized by the efficiency of their incorporation into the micellar fraction in the gut. The fate of a compound from its presence in food to its absorbable form is affected by many factors that must be known in order to understand and predict the efficiency of a compound s bioaccessibility and bioavailability from a certain meal. ... 

Bioavailability is defined as the portion or fraction of a chemical that is available for biological action and is influenced by several factors including the molecular size and charge of a molecule, structural features of membranes, first pass metabolism, and therefore, bio availability can be influenced by the molecular structure of a chemical. This situation presents an opportunity for molecular designers to manipulate a chemical s structure to decrease bioavailability and consequently hazard. If the availability of a molecule can be decreased, the amount of chemical at the site of action is decreased which leads to decreased toxicity. 

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. 

Whenever a drug is administered by an extra-vascular route, there is a danger that part of the dose may not reach the blood (i.e., absorption may not be complete). When the intravenous route is used, the drug is placed directly in the blood therefore an IV injection is, by definition, 100% absorbed. The absolute bioavailability of an extravascular dosage form is defined relative to an IV injection. If IV data are not available, the relative bioavailability may be defined relative to a standard dosage form. For example, the bioavailability of a tablet may be defined relative to an oral solution of the drug. 

Bioavailability depends not only on having the drug in solution, but also on the drug s permeability. A jejunal permeability of at least 2-4 x 10 4cm/s, measured in human subjects by intubation, is considered high [97]. For many drugs and other substances, this permeability corresponds to a fraction absorbed of 90% or better. Amidon et al. [97] thus proposed a Biopharmaceutics Classification System (BCS) for drugs based on the above definitions of these two parameters. Table 3 defines the BCS and includes some drugs representative of each class. 

U.S. EPA defines MNA as the reliance on natural processes, within the context of a carefully controlled and monitored site cleanup approach, to achieve site-specific remediation objectives within a time frame that is reasonable compared to that offered by other more active methods. The natural processes include biodegradation, dispersion, dilution, sorption, volatilization, stabilization, and transformation. These processes reduce site risk by transforming contaminants to less toxic forms, reducing contaminant concentrations, and reducing contaminant mobility and bioavailability. Other terms for natural attenuation in the literature include intrinsic remediation, intrinsic bio-remediation, passive bioremediation natural recovery, and natural assimilation. 30... 

Physical and Chemical Properties. The physical and chemical properties of lead and its compounds are sufficiently well defined to allow an estimation of the environmental fate of lead to be made (Howe 1981 HSDB 1996 Lide 1996 Merck 1989 Sax 1984 Sax and Lewis 1987). Availabilities of the various forms need to be modeled and the connectivities to bioaccessabilities and bioavailabilities determined. 

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