Population pharmacokinetic modeling of sustained release lithium in the serum, erythrocytes and urine of patients with bipolar disorder.

Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of srLi, administered once a day, in adults. The present study describes srLi PK in the serum and erythrocytes of bipolar patients. To assess srLi PK, we studied prospectively 17 French bipolar patients on a median dose of 1000 mg (600-1600) for at least 2 years. Serum (S), erythrocyte (E) concentrations, and urinary (U) amount were collected over 8 h after 15 days of morning intake using monitoring electronic medical system (MEMs). Population PK parameters were estimated using the SAEM algorithm (MONOLIX 4.3.3 software). Using a population approach, we built a PK population model of srLi including one S compartment (V 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 erythrocyte over serum and its between-subject variability (BSV).