Lithium - Pharmacokinetics
The digestive absorption of lithium is complete and the maximum plasma concentration is observed two to four hours after an oral intake of a non sustained release form.
The average plasma half-life of lithium is about 22 hours. Its plasma level at steady state regarded as therapeutically effective ranges from 0.5 to 0. 8 mmol/L. When blood sampling is performed in the morning before the first daily intake or in the evening before the single intake of a sustained-release formulation the plasma level should be between 0.8 and 1.2 mmol/liter.
Its volume of distribution is close to 0.8 L/kg corresponding to a very broad distribution, approximately equal to that of total water. Although lithium is not bound to plasma proteins, its transfer into the brain and the cerebrospinal fluid is slow, and at equilibrium, the cerebrospinal fluid contains approximately 40% of the plasma concentration.
The elimination is more than 95% urinary and any renal impairment delays it. Approximately 80% of lithium filtered by the glomerulus is reabsorbed from the proximal tubule; its clearance is approximately 20% of that of creatinine. A decrease of sodium intake increases lithium retention by the kidney and conversely. Thiazide diuretics, nonsteroidal antiinflammatory drugs, ACE inhibitors reduce its renal elimination and increase its plasma concentration.
Studies comparing plasma and erythocytic concentrations of lithium gave conflicting results for predicting its clinical efficacy and the determination of lithium in erythrocytes seems without clinical interest.
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