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

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 ha...

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Published in:European Journal of Clinical Pharmacology Vol. 75; no. 4; pp. 519 - 529
Main Authors: Couffignal, C., Bertrand, J., Sportiche, S., Jarroir, Marine, El Balkhi, S., Djebrani-Oussedik, N., Poupon, J., Declèves, X., Mentré, F., Bellivier, F.
Format: research tables/charts Journal Article
Published: Springer Nature Apr2019
Online Access:View this record in EBSCOhost
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      dt: Apr2019
      vid: 75
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-018-2605-3
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        atl: Population pharmacokinetic modeling of sustained release lithium in the serum, erythrocytes and urine of patients with bipolar disorder.
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        au:
          Couffignal, C.
          Bertrand, J.
          Sportiche, S.
          Jarroir, Marine
          El Balkhi, S.
          Djebrani-Oussedik, N.
          Poupon, J.
          Declèves, X.
          Mentré, F.
          Bellivier, F.
        affil: Département de Biostatistique, AP-HP, HUPNVS, 46 rue Henri Huchard, 75877, Paris Cedex 18, France
      sug:
        subj:
          Bipolar Disorder Drug Therapy
          Lithium Pharmacokinetics
          Delayed-Action Preparations Pharmacokinetics
          Human
          Adult
          France
          Lithium Administration and Dosage
          Lithium Blood
          Lithium Urine
          Erythrocytes Drug Effects
          Population Health
          Algorithms Utilization
          Monitoring, Physiologic
          Models, Biological
          Computer Simulation
          Record Review
          Adult: 19-44 years
      ab: 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).
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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