Lithium: Updated Human Knowledge Using an Evidence-Based Approach

  title={Lithium: Updated Human Knowledge Using an Evidence-Based Approach},
  author={Etienne Marc Grandjean and Jean-Michel Aubry},
  journal={CNS Drugs},
After a single dose, lithium, usually given as carbonate, reaches a peak plasma concentration at 1.0–2.0 hours for standard-release dosage forms, and 4–5 hours for sustained-release forms. Its bioavailability is 80–100%, its total clearance 10–40 mL/min and its elimination half-life is 18–36 hours. Use of the sustained-release formulation results in 30–50% reductions in peak plasma concentrations without major changes in the area under the plasma concentration curve.Lithium distribution to the… 
Population pharmacokinetic modeling of sustained release lithium in the serum, erythrocytes and urine of patients with bipolar disorder
This is a PK model of srLi once a day in bipolar patients using a population approach simultaneously describing Li concentrations in serum, erythrocytes, and urine which provide an estimate of the ratio of concentration in ery Throcyte over serum and its between-subject variability (BSV).
Prediction Model of Serum Lithium Concentrations.
Serum concentrations of lithium can be predicted from oral dosage with high precision, using the proposed model, using creatinine clearance-based lithium clearance (Li-CL).
Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder
The results demonstrate the nonlinear renal excretion of lithium; hence, dosage adjustments are recommended for patients with renal insufficiency, and a PPK model for lithium was developed.
Population Pharmacokinetics of Lithium in Young Pediatric Patients With Intellectual Disability
The lithium PK properties in young children were similar to those in older children and adults, and the proposed model can be used for further PK/PD analysis to optimize the dosage regimen of lithium in children.
Population pharmacokinetic model of lithium and drug compliance assessment
Comparative Pharmacokinetic Analysis of а Novel Prolonged Release Dosage Form of Lithium Citrate in Mice
Performed research has proven that combining aluminium oxide and organosilicone polymer as supportive components with lithium citrate helps to maintaining a stable lithium ions concentration in blood and brain which is important for achieving positive lithium therapy effect.
Pharmacokinetics of Lithium in Egyptian Bipolar Patients: Dosage Adjustment Approach
A pharmacokinetic model is developed for the estimation of lithium clearance in Egyptian bipolar patients and can be used afterwards during dosage adjustment to achieve target’s steady-state plasma concentrations in similar settings.
Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning.
Investigating differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns suggests that differences in Plasma and brain kinetics may at least partially explain the observed variability betweenhuman intoxication patterns.
Population Pharmacokinetic Analyses of Lithium: A Systematic Review
A literature search was conducted from PubMed database from inception to December, 2016 and the significant predictors of lithium clearance identified in most studies were renal function and body size, which are summarized and discussed in this review.


The pharmacokinetics of lithium in normal humans: expected and unexpected observations in view of basic kinetic principles.
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, and 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).
Pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients after acute dosage
  • D. Thornhill
  • Medicine
    European Journal of Clinical Pharmacology
  • 2004
In healthy volunteers the ordinary preparation was completely absorbed but only 85% of the sustained-release form was absorbed in the manic subjects, and lithium ion distributed into two kinetic compartments and the final compartment appeared to correspond to total body water.
Renal reactions to changes of lithium dosage.
The renal function was assessed in 51 bipolar patients on multiple-dosage lithium maintenance therapy from 1 to 22 years, after placing them on single (HS) dosage for 12-18 months, confirming the beneficial renal reaction to single-dose posology, as well the female sensitivity to Li therapy in general and especially with concomitant antipsychotic medication.
Gabapentin does not alter single-dose lithium pharmacokinetics.
The data indicate that gabapentin treatment at this high therapeutic dose does not cause clinically significant alterations in short-term Li pharmacokinetics in patients with normal renal function, and suggest that these two medications may be administered in combination for the management of bipolar disorder.
Steady-state pharmacokinetics of lithium in healthy volunteers receiving concomitant meloxicam.
Meloxicam (15 mg) moderately increased the plasma concentration of lithium in healthy volunteers, but by a magnitude thought to be of low clinical relevance, Nevertheless, lithium plasma concentrations should be closely monitored in patients receiving concomitant meloxicam and lithium therapy.
Tenidap sodium decreases renal clearance and increases steady-state concentrations of lithium in healthy volunteers.
It is recommended that serum lithium levels be monitored when tenidap and lithium are administered concomitantly, because of the significant differences in renal clearance and steady-state concentrations.
Increased lithium serum and red blood cell concentrations during ketorolac coadministration.
The objective of the study presented here was to determine significant changes in lithium serum and red blood cell (RBC) concentrations after lithium and ketorolac (oral formulation) coadministration at steady-state conditions.
Evaluation of the interaction of lithium and alprazolam.
The results of this study do not support a definitive interaction of lithium and alprazolam and there is little clinical significance to the small rise in serum lithium concentrations.
Effect of over-the-counter dosages of naproxen sodium and acetaminophen on plasma lithium concentrations in normal volunteers.
The results of this study demonstrated that OTC doses of naproxen sodium and acetaminophen did not increase plasma lithium concentrations in these volunteers when taken for short periods of time.
Pharmacokinetics of lithium carbonate in children.
On the whole, the pharmacokinetics of lithium in children had the same features as in adults, with a trend toward a shorter elimination half-life and higher total clearance.