Lithium tissues distribution

The microlocalisation technique with the stable isotope Li uses a beam of neutrons in an atomic reactor. The Li nucleus absorbs a neutron and immediately undergoes fission to produce an a-particle and a H atom, which create tracks in a suitable detector placed in contact with Li-containing tissue. The tissue distribution in the rat, brain lithium distribution in the mouse " and the rat, ° distribution in the mouse embryo, kinetics in the mouse brain, and distribution in mutant strains of mice with dysmyelination have been studied. 

Schou, M., Lithium studies. 3. Distribution between serum and tissues. Acta Pharmacol. Toxicol. 15, 115-124 (1958). 

Some drugs such as digoxin and lithium take several hours to distribute to tissues. Digoxin samples should be taken at least 6 hours after the last dose and lithium just before the next dose (usually 24 hours after the last dose). Aminoglycosides distribute quite rapidly, but it is still prudent to wait 1 hour after giving the dose before taking a sample. 

Lithium is readily absorbed from the gastrointestinal tract and completely distributed throughout all the tissues in the body. During an acute manic episode, achieving blood serum concentrations between 1.0 and 1.4 mEq/L is desirable. Maintenance doses are somewhat lower, and serum concentrations that range from 0.5 to 1.3 mEq/L are optimal. 

Because lithium is not bound to any plasma or tissue proteins, it is widely distributed throughout the body. Lithium ions are eliminated mainly by the kidneys. There is a direct relationship between the amount of sodium chloride ingested and the fraction of filtered lithium resorbed, in that, the lower the sodium intake, the greater is the lithium retention. The contraindications are significant cardiovascular or renal diseases that would compromise its excretion. 

Tissue lithium distribution in rat after chronic administration of 1 mmol/kg in drinking fluid... 

A lithium NMR study has been made of lithium atoms adsorbed on a Si(lll)-(3 x 1)-Li surface.634 23Na and 35C1 NMR spectra were used to probe the distribution and state of Na+ and Cl ions in tissues.635... 

Among 16 different tissue samples from goats fed with lithium-poor rations, blood serum was found to reflect the lithium status best, followed by hair and milk (Arn-hold 1989, Anke etal. 1991). The lithium content of ruminant organs appeared to be species- and site-specific (Arnhold and Anke 1987). The distribution of lithium among rat tissues has been described by Pickett and O Dell (1992), with the highest concentration being found in tibial bone, though this lost most of its lithium when the rats were fed a low-lithium diet. 

Lithium is not appreciably bound to serum proteins, and is distributed throughout the body. The drug appears to concentrate in fatty tissues such as bone, thyroid and brain. 

Figure 1 The distribution of lithium in a range of tissues following chronic administration in rats...

One of the problems in the study of lithium action is the lack of precision in localisation of the ion and in the measurement of its movements between cells and between tissues. This lack of precision arises partly because lithium is a very mobile ion, partly because of its widespread distribution in the body, and partly because of the difficulties of lithium analysis. Analytical problems generally stem... 

B. Pharmacokinetics. Lithium is completely absorbed within 6-8 hours of ingestion. The initial volume of distribution (Vd) is about 0.5 L/kg, with slow entry into tissues and a final Vd of 0.7-0.9 L/kg. Entry into the brain is slow, which explains the delay between peak blood levels and central nervous system (ONS) effects after an acute overdose. Elimination is virtually entirely by the kidney, with a half-life of 14-30 hours. 

A. Acute ingestion may cause initial mild nausea and vomiting, but systemic signs of intoxication are minimal and usually are delayed for several hours while lithium distributes into tissues. Initially high semm levels fall by 50-70% or more with tissue equilibration. 

Early studies showed that lithium is widely distributed in tissues following oral administration or by intraperitoneal or intravenous injection to experimental animals (for review, see Refs. 12 and 17). Thellier et al., in a series of elegant neutron activation experiments using the isotope Li, provided visual localization of lithium in the whole body [18] and in different areas of the brain [8]. Of the soft tissues the pituitary, the thymus, and, most particularly, the thyroid glands have more than the average accumulation of lithium. Bone also appears to accumulate lithium. 

Until 1950, 13 mineral elements were classified as essential these comprised the major elements (calcium, phosphorus, potassium, sodium, chlorine, sulphur, magnesium) and the micro or trace elements (iron, iodine, copper, manganese, zinc and cobalt). By 1970, molybdenum, selenium, chromium and fluorine had been added to the list subsequently, arsenic, boron, lead, lithium, nickel, silicon, tin, vanadium, rubidium and aluminium have also been included, the list varying slightly according to the different authorities. Plant and animal tissues contain a further 30 mineral elements, in small quantities, for which no essential function has been found. They may be acquired from the environment, but it has been suggested that as many as 40 or more elements may have metabolic roles in mammalian tissues. Fortunately, many of these trace elements, especially those of more recent discovery, are required in such minute quantities, or are so widely distributed in foods for animals, that deficiencies are likely to be extremely rare under normal practical conditions. 

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