Systemic bioavailability

Presystemic elimination diminishes the bioavailability of a drug after its oral administration. Absolute bioavailability = systemically available amount/ dose administered relative bioavailability = availability of a drug contained in a test preparation with reference to a standard preparation. 

R. Seemayer etal, US Patent 6,613,918 (September 2, 2003) Assignee Bioavailability Systems, LLC. 

Receptor Topical Skin Oral Bioavailability Systemic Clearance Half-Life (h)... 

Nicardipine is almost completely absorbed after po adrninistration. Administration of food decreases absorption. It undergoes extensive first-pass metaboHsm in the Hver. Systemic availabiHty is dose-dependent because of saturation of hepatic metaboHc pathways. A 30 mg dose is - 35% bioavailable. Nicardipine is highly protein bound (>95%). Peak plasma concentrations are achieved in 0.5—2.0 h. The principal path of elimination is by hepatic metaboHsm by hydrolysis and oxidation. The metaboHtes are relatively inactive and exert no pharmacological activity. The elimination half-life is 8.6 h. About 60% of the dose is excreted in the urine as metaboHtes (<1% as intact dmg) and 35% as metaboHtes in the feces (1,2,98,99). 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

First-pass metabolism is the elimination of an orally administed drug by the liver or sometimes the gut wall, before it reaches the systemic circulation. First-pass metabolism results in a decreased systemic bioavailability. 

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

Recently, leaders in the pharmaceutical industry have developed a list of desired properties for a fourth generation of SERMs (Table 2). In general, future SERMs must oppose endogenous hormone action in the breast and reproductive system while displaying full estrogenic effects in the cardiovasculature, bone and central nervous systems. Additional criteria are that fourth generation compounds possess superior bioavailability compared with existing SERMs and have... 

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

Fisher NS, Reinfelder JR (1995) The trophic transfer of metals in marine systems. In Tessier A, Turner DR (eds) Metal speciation and bioavailability in aquatic systems. Wiley, Chichester, p 363... 

The mucosa of the GIT represents an interface between the external and internal environments. The expansive surface area is necessary for the efficient hydrolysis of foodstuffs and the absorption of energy and nutrients. The mucosa also influences the systemic availability of non-nutrient compounds in the diet, both beneficial and detrimental. Digestion and absorption of glucosinolates are critical determinants of health benefits (see Chapter 4) Similarly, the bioavailability and health benefits of phytoestrogens, such as genistein (see Chapters 5 and 10) are at least partly dependent on the carrier-mediated processes of absorption associated with the GIT (Oitate et al, 2001). Moreover, the metabolic activities of the mucosa can influence the systemic concentrations and forms of dietary phytochemicals, as exemplified by research with soy isoflavones (Andlauer et al., 2000). 

McDougall, G.J. et al.. Assessing potential bioavailability of raspberry anthocyanins using an in vitro digestion system, J. Agric. Food Chem., 53, 5896, 2005. 

Xenobiotics exist not only in the free state but also in association with organic and mineral components of particles in the water mass, and the soil and sediment phases. This association is a central determinant of the persistence of xenobiotics in the environment, since the extent to which the reactions are reversible is generally unknown. Such residues may therefore be inaccessible to microbial attack and apparently persistent. This is a critical factor in determining the effectiveness of bioremediation (Harkness et al. 1993). Although the most persuasive evidence for the significance of reduced bioavailability comes from data on the persistence of agrochemicals in terrestrial systems (Calderbank 1989), the principles can be translated with modification to aquatic and sediment phases that contain organic matter that resembles structurally that of soils. 

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. 

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