Gastrointestinal Absorption of Lithium

The absorption of lithium by the gut has not been widely studied. The pharmacokinetic mechanisms have clinical significance, however, because of the use of differing formulations and treatment regimes, each with its own apparent advantage. Early studies indicated a passive mode of absorption (163). Two types of study have recently ex- 

Absorption of lithium from guinea pig jejunum has been studied using an isolated mucosal preparation from which the underlying mus-cularis mucosae has been stripped (164). Absorption was shown to occur via a paracellular route and was unaffected by metabolic inhibitors or antidepressant, neuroleptic, or antiinflammatory drugs (165-167). These findings confirmed earlier work using everted sacs prepared from rat intestine (168, 169). The passive nature of lithium uptake into both kidney slices and isolated guinea pig intestinal epithelial cells has also been reported (170, 171). 

Using isolated intact epithelial mucosal preparations, we have shown that, when lithium associated with the extracellular space was taken into account, acute cellular uptake of lithium was negligible (172). This is confirmed by experiments on lithium efflux from everted rings of rat jejunum (173). The recognition that intestinal uptake and transport of lithium may not involve transcellular transport of the metal agrees with proposed transport mechanisms for other alkali metals and magnesium (174). Metal-ion carrier proteins are not essential for rapid absorption of metals to occur their function is to assist when existing equilibrium conditions are unfavorable. 

Routine serum lithium estimations on blood taken 12 hr after the previous dose give no indication of the peak serum lithium concentrations. These usually occur within 4 hr of the dose and are associated with any transient side effects that may occur (50). The pharmacokinetics of lithium preparations is studied by administration of a single test dose of the drug followed by timed sequential blood lithium determinations. Such studies are of interest for the following reasons  

Pharmacokinetic studies allow the selection of a drug formulation with maximum bioavailability (175). 

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Na, K -ATPase Sodium-Potassium Cotransport Lithium and Immunology Gastrointestinal Absorption of Lithium... 

Davie RJ (1991) Gastrointestinal absorption of lithium. In Birch NJ, ed. Lithium and the Cell Pharmacology and Toxicology, pp. 243 - 248. 

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... 

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]. 

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. 

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. 

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