Biological Distribution

In a study of psychiatric patients after 1 week of lithium treatment, the serum Li+ level was typically 1 mM, whereas in brain and muscle the levels were 0.4 and 0.5 mM, respectively. Within the brain itself, the distribution of Li+ appears to be uneven however no particular region appears to accumulate Li+ to any significant extent [47]. It has been 

The distribution of Li+ in vivo is primarily due to the relative rates of entry and efflux of the cation in the different tissues. The uptake of Li+ from the blood is relatively rapid into the kidney and is slower into the liver, bone, and muscle. The movement of Li+ both into and out of the brain is very slow compared to other organs and this is thought to be due to the low permeability of the blood-brain barrier for this cation [50]. 

Following oral administration, the intestinal absorption of Li+ occurs primarily in the small intestine and the subsequent movement of Li+ into the blood stream is a passive process, via a paracellular route, with very little Li+ accumulating in the intestinal cells [51,52]. The excretion of Li+ is almost entirely by the kidneys with only very small amounts ( 1%) being excreted in the feces, sputum, sperm, and sweat. The elimination half-life of Li+ is approximately 20-30 hours. 

Most human cells are exposed to less than 2 mM Li+, and in most tissues the intracellular Li+ concentration is lower than the extracellular concentration. The level inside cells is generally below that expected for the passive diffusion of the Li+ ion across the cell membrane, indicating that Li+ is actively transported out of cells. For instance, the concentration of Li+ inside the erythrocytes from people taking lithium salts is low with a typical ratio of intra- to extracellular Li+ of 0.5 [53]. 

The transport behavior of Li+ across membranes has been the focus of numerous studies, the bulk of which have concentrated upon the human erythrocyte for which the Li+ transport pathways have been elucidated and are summarized below. The movement of Li+ across cell membranes is mediated by transport systems which normally transport other ions, therefore the normal intracellular and subcellular electrolyte balance is likely to be disturbed by this extra cation. Additionally, Li+ has been shown to increase membrane phospholipid unsaturation in rat brain, leading to enhanced fluidity in the membrane, which could have repercussions for membrane-associated proteins and for membrane transport properties. 

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The only commonly used radioisotope in this class is used in small (- IS.S MBq (500 -lCi) injected dose) quantities as a diagnostic for the evaluation of thyroid function. The compound is adininistered as Nal and these procedures are only possible owing to the favorable biological distribution of iodide. Up to 25% of the entire injected dose of iodide is accumulated in the thyroid with a very slow washout the rest is rapidly excreted in the urine. No other compound exhibits so high a ratio of concentration in a target tissue to that of other tissues. 

Sangster, J. Octanol-Water Partition Coefficients Fundamentals and Physical Chemistry, Wiley, Chichester, 1997. n Valko, K. Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution. J. Chromatogr. A 2004, 1037, 299-310. 

Addition of sufficient base to give a > 3 to a ferric solution immediately leads to precipitation of a poorly ordered, amorphous, red-brown ferric hydroxide precipitate. This synthetic precipitate resembles the mineral ferrihydrite, and also shows some similarity to the iron oxyhydroxide core of ferritin (see Chapter 6). Ferrihydrite can be considered as the least stable but most reactive form of iron(III), the group name for amorphous phases with large specific surface areas (>340 m2 /g). We will discuss the transformation of ferrihydrite into other more-crystalline products such as goethite and haematite shortly, but we begin with some remarks concerning the biological distribution and structure of ferrihydrite (Jambor and Dutrizac, 1998). 

Chand N, Eyre P Classification and biological distribution of histamine receptor subtypes. Agents Actions 1975 5 277-295. 

In theory, an isosteric/isoelectronic aromatic ring replacement within a toxic or therapeutic molecule should lead to a retention of biological activity. The fact that this is sometimes not observed may mean either that the activity is heterocycle-specific or that unforseen changes in metabolism, biological distribution and excretion, partition coefficient or stability have accompanied the molecular change. In such cases, activity may be observed in in vitro assays while not being observed in vivo (cf. the possible case of the dithiin analogue of TCDD in Table 3). 

Due to its central role in oxidative phosphorylation, cytochrome oxidase has a wide biological distribution. It is present in all animals and plants, in aerobic yeasts and in some bacteria. It is an integral membrane protein, being firmly associated with the inner membrane of mitochondria, the respiratory organelle of eukaryotic organisms, or, in bacteria the plasma membrane (Malstrom, 1990). 

Protein family Biologic distribution Main biologic function Preferred Substrate (cleavage site) References... 

The biological distribution of the [ " Tc(diars)2X2] series in rats has also been determined, as well as the biological distribution of [ "Tc(diars)2Br2] and of o Tl in dogs. 

Hukkanen, E.J. A Systems Approach to the Modeling and Control of Molecular, Microparticle, and Biological Distributions. Ph.D. thesis. University of Illinois at Urbana-Champaign Illinois, 2004. 

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