The pharmacokinetics of lithium in normal humans: expected and unexpected observations in view of basic kinetic...

Lithium (Li+) does not undergo metabolism, is unbound to proteins from plasma, and excreted in major part by the kidney. We studied the disposition of single doses of Li+ given orally to 5 normal subjects, once as a conventional form and once as a slow release form. Renal clearances of Li+ were lower during night time, plasma clearances were 22 to 43 ml/min when not corrected for urinary recovery and 21 to 28 ml/min when corrected. Urinary recovery (measured on 96 hours) was 65.0 to 99.7% and was individually less stable than plasma clearance. Other observations that might have clinical relevance were that the rate of Li+ absorption from the digestive tract varied more from one subject to another than between the two pharmaceutical forms, that the 24 hours renal clearance and the extend of urinary recovery on 96 hours could not be predicted from short term measurements of Li+ (in urine and plasma), and that the known circadian changes in the rate of Li+ elimination were confirmed.