Pharmacokinetics and Therapeutic Drug Monitoring

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.

The elimination half-life of Li+ is estimated at 24 hours, and more than 90% of the dose of Li+ is excreted into the urine. Renal clearance, however, is only 20%, since Li+ is actively reabsorbed in the proximal tubule at sites normally used for the conservation of Na+.Thus, competition between Li+ and Na+ for uptake sites can alter the elimination of Li+ and its concentration in total body water. Na+ loading enhances Li+ clearance, while Na+ depletion promotes Li+ retention. This important relationship explains the appearance of Li+ toxicity (discussed later) associated with diet (low Na+),


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