Gastrointestinal tract lithium

Lithium salts, generally in the form of the carbonate or bicarbonate, are rapidly absorbed from the gastrointestinal tract and reach a peak plasma concentration after 2- hours. Extreme fluctuations in blood lithium levels, which are associated with side effects such as nausea, diarrhoea and abdominal cramp, are reduced by using sustained release preparations. Lithium is not protein bound and therefore is widely distributed throughout the body water, which accounts for the adverse effects it has on most organ systems should it reach toxic levels. To avoid toxicity, and ensure optimal... 

Lithium is readily absorbed from the gastrointestinal tract, reaching a peak plasma level in 2 to 4 hours. Distribution occurs throughout the extracellular fluid with no evidence of protein binding. Passage through the blood-brain barrier is limited, so that cerebrospinal fluid levels are 50% of plasma levels at steady state. 

Lithium carbonate is completely absorbed by the gastrointestinal tract and reaches peak plasma levels in 1-2 hours. The elimination half-life is approximately 24 hours. Steady-state lithium levels are achieved in approximately 5 days. Therapeutic plasma levels range from 0.5 to 1.2 mEq/L. Lower plasma levels are associated with less troubling side effects, but levels of at least 0.8 mEq/L are often required in the treatment of acute manic episodes. Therefore, when intolerable side effects have not intervened, treatment of acute mania with lithium should not be considered a failure until plasma levels of 1.0-1.2 mEq/L have been reached and have been maintained for 2 weeks. As discussed at the end of this chapter (see Treatment of Mania or Mixed Episodes ), more severely ill patients may require combination treatment. 

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. 

Ionized lithium is readily absorbed from the gastrointestinal tract and is excreted almost entirely by the kidney, which ordinarily clears it at a rate of about one-quarter to that of creatinine clearance (53). 

As might be expected, the presence of food in the gastrointestinal tract has been shown to affect lithium absorption and a diurnal variation in renal lithium clearance has been reported 183, 184). In our experiments, diurnal and other factors appeared to influence lithium pharmacokinetics to a greater degree than did formulation differences 182). We conclude that the practice of administering an early evening dose after a meal may delay the lithium peak sufficiently to reduce the possible discomfort of any transient side effects and may improve patient compliance. This is more important than the choice of preparation to be given. 

The most common preparations of lithium salts arc carbonates (lithium carbonate, or Li2CO,), which are prepared in tablet form. In terms of pharmacokinetics, lithium, which is taken orally, is ab.sorbed completely from the gastrointestinal tract (primarily the small intestine) and distributed throughout the system. The lithium is distributed in the body water and is not metabolized. Excretion occurs almo.st entirely by the kidneys, with between 90% and 95% eliminated through urine. 

Saliva is not an important route of excretion since most of the chemicals present in saliva will eventually reach the gastrointestinal tract to be reabsorbed or eliminated in the feces. The unbound fraction of several therapeutic drugs may diffuse passively from plasma into saliva. This provides a noninvasive means of indirectly monitoring plasma concentrations of drugs like lithium, phenytoin, and theophylline. Metals like lead, cadmium, and mercury are also present in saliva. 

Absorption of lithium from the gastrointestinal tract is complete, with peak plasma concentration reached 2 to 4 hours after an oral dose. This cation does not bind to protein. Lithium elimination is biphasic during the first phase, 30% to 40% of the dose of lithium is cleared, with an... 

D. Enhancement of Elimination Enhancement of elimination is possible for a number of toxins, including manipulation of urine pH to accelerate renal excretion of weak acids and bases. For example, alkaline diuresis is effective in toxicity due to fluoride, isoniazid, fluoroquinolones, phenobarbital, and salicylates. Urinary acidiflcation may be useful in toxicity due to weak bases, including amphetamines, nicotine, and phencyclidine, but care must be taken to avoid acidosis and renal failure in rhabdomyolysis. Hemodialysis or hemoperfusion enhances the elimination of many toxic compounds, including acetaminophen, ethylene glycol, formaldehyde, lithium, methanol, procainamide, quinidine, salicylates, and theophylline. Cathartics such as sorbitol (70%) may decrease absorption and hasten removal of toxins from the gastrointestinal tract. 

A number of studies of the mucosal mechanisms of lithium absorption in the gastrointestinal tract have shown that lithium [28,29], and indeed other metals [30-32], transfers across the tract not by passage through the cell but by paracellular transport via the tight junctions and pericellular spaces. Cellular transport mechanisms and carriers identified in cells may thus exist only for the domestic requirements of the intestinal cells themselves, which in turn protect their own milieu interieur by, as far as practicable, avoiding accumulation of externally derived metals [33]. 

Lithium is readily absorbed from the gastrointestinal (GI) tract. Food or antacids (Goode et ah, 1984) do... 

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