Bioavailability tissue

VI. BIOAVAILABILITY, TISSUE DISTRIBUTION, METABOLISM, AND SAFETY OF LYCOPENE... 

Jain, C.K., Agarwal, S., and Rao, A.V. 1999. The effect of dietary lycopene on bioavailability, tissue distribution, in-vivo antioxidant properties and colonic preneoplasia in rats. Nutr. Res. 19, 1383-1391. 

While broad spectrum anthelmintics (macrolide endectocides, benzimidazole carbamates, tetrahydropyrimidines) largely overlap in the range of endoparasites (mainly nematodes) they affect, the various anthelmintic classes (based on chemical structure) differ in mechanism of action, degree of activity and in pharmacokinetic properties (bioavailability, tissue distribution and... 

Anadon, A. Martinez, M.A. Martinez, M. De La Cruz, C. Diaz, M.J. Martinez-Larranaga, M.R. Oral bioavailability, tissue distribution and depletion of flumequine in the food producing animal, chicken for fattening. Food Chem. Toxicol. 2008, 46, 662-670. 

Lipophilicity is another molecular characteristic of a compound that often dictates biological properties including the compound oral bioavailability, tissue distribution, cellular uptake, receptor binding, metabolism, and excretion. The most commonly used measure of lipophilicity is the logarithm of the 1-octanol/water partition coefficient (log Hence, computational... 

One of the most popular orally active penicillins in present clinical use is amoxicillin (12). Its oral effectiveness and broad spectrum of activity against common pathogens as well as its better absorption than its closest precedent competitor, ampicillin (14), largely accounts for this. Higher blood and tissue levels of antibiotics is another means of dealing with resistance. In an attempt to achieve yet further improvements in oral bioavailability and hence blood and ti.ssue levels of amoxicillin, the prodmg fumoxicillin (13) is prepared from amoxicillin (12) by treatment with furfural [3]. The imine moiety is less basic than the primary amine so that the isoelectric point of fumoxicillin is more on the acid side than is that of amoxicillin. 

Most ACE inhibitors are prodrugs, with the exceptions of captopril, lisinopril, and ceranapril. Prodrugs exert improved oral bioavailability, but need to be converted to active compounds in the liver, kidney, and/or intestinal tract. In effect, converting enzyme inhibitors have quite different kinetic profiles with regard to half time, onset and duration of action, or tissue penetration. 

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]. 

Polymeric microparticles have been studied and developed for several years. Their contribution in the pharmacy field is of utmost importance in order to improve the efficiency of oral delivery of drugs. As drug carriers, polymer-based microparticles may avoid the early degradation of active molecules in undesirable sites of the gastrointestinal tract, mask unpleasant taste of drugs, reduce doses and side effects and improve bioavailability. Also, they allow the production of site-specific drug targeting, which consists of a suitable approach for the delivery of active molecules into desired tissues or cells in order to increase their efficiency. 

The absorption and transport processes of many of the phytochemicals present in food are complex and not fully understood, and prediction of their bioavailability is problematic. This is particularly true of the lipid-soluble phytochemicals. In this chapter the measurement of carotenoid bioavailability will be discussed. The carotenoids serve as an excellent example of where too little understanding of food structure, the complexity of their behaviour in foods and human tissues, and the nature and cause of widely different individual response to similar intakes, can lead to misinterpretation of study results and confusion in our understanding of the relevance of these (and other) compounds to human health. 

All the actual or putative functional benefits of carotenoids are dependent on their bioavailability amounts consumed, amounts released from the food structure during digestion and extent of absorption and tissue distribution. The following three sections deal with each of these issues in turn. 

The release of a compound from the food matrix in which it is incorporated is a determining process for its bioavailability and is largely influenced by the physicochemical characteristics of the compound, the type of food matrix, the subcellular location of the compound in plant tissues, and the food processing. The, food matrix type greatly influences the compound bioaccessibility. 

These agents have broad-spectrum activity against both gram-negative and gram-positive bacteria. They provide high urine and tissue concentrations and are actively secreted in reduced renal function. Switch to oral when possible due to excellent bioavailability. 

Alkoxyalkanoate esters have been used as prodrugs to improve the oral bioavailability of antiviral agents such as (+)-cyclaradine (carbocyclic arabino-furanosyl adenine) [41]. (+)-Cyclaradine has been shown to be effective against herpes simplex virus in tissue culture at noncytotoxic concentrations. Two prodrugs of (+)-cyclaradine, namely, (+)-cyclaradine-5 -methoxyacetate (CM) and (+)-cyclaradine-5,-ethoxypropionate (CE) (Fig. 2), may be promising candidates... 

Bioavailability was assessed from measurement of the area under the curve (AUC) of whole blood lead concentration vs time (Blood AUC) or from measurements of the lead concentrations in bone, kidney or liver (the arithmetic mean of the three tissues is shown in the table). Data are from Casteel et al. (1997) and EPA (1996a, 1996b, 1996c). 

Lead was found to decrease tissue levels of vitamin C in a study in rats (Vij et al. 1998). Since vitamin C is required for the synthesis of heme, the authors suggested that some hematological effects of lead (e.g., inhibition of ALAD) may be due at least partially to a lead-induced decrease in bioavailability or increased demand of vitamin C. Supplementation with vitamin C almost completely restored ALAD activity in blood and liver. 

---