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Eur J Clin Pharmacol. 2019 Apr;75(4):519-528. doi: 10.1007/s00228-018-2605-3. Epub 2018 Dec 15.

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

Author information

1
Département de Biostatistique, AP-HP, HUPNVS, 46 rue Henri Huchard, 75877, Paris Cedex 18, France. camille.couffignal@aphp.fr.
2
UMR 1137, Université Paris Diderot, IAME, Sorbonne Paris Cité, Paris, France. camille.couffignal@aphp.fr.
3
UMR 1137, INSERM, IAME, Paris, France. camille.couffignal@aphp.fr.
4
UMR 1137, Université Paris Diderot, IAME, Sorbonne Paris Cité, Paris, France.
5
UMR 1137, INSERM, IAME, Paris, France.
6
Département de Psychiatrie et de Médecine Addictologique, AP-HP, HUSLS-LRB-FWD, Paris, France.
7
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
8
UMR-S1144, INSERM, Paris, France.
9
Service de Pharmacologie - Toxicologie et Pharmacovigilance, CHU Limoges, Limoges, France.
10
Département de Pharmacologie-toxicologie, AP-HP, HUSLS-LRB-FWD, Paris, France.
11
Département Biologie du Médicament et Toxicologie, APHP, HUPC, Paris, France.
12
UMR-S1144, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
13
Département de Biostatistique, AP-HP, HUPNVS, 46 rue Henri Huchard, 75877, Paris Cedex 18, France.

Abstract

PURPOSE:

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.

METHODS:

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).

RESULTS:

Using a population approach, we built a PK population model of srLi including one S compartment (VS = 23.0 L, ClS = 1.21 L h-1), one E compartment (VE = 64.7 L, ClSE = 3.63 L h-1, ClES = 9.46 L h-1), and one U compartment (F = 0.62) and estimate the ratio of concentrations to Li in E over S at 0.38 with 27% between-subject variability.

CONCLUSION:

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).

KEYWORDS:

Bipolar disorder; Lithium; Pharmacokinetics; Sustained release

PMID:
30554270
DOI:
10.1007/s00228-018-2605-3

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