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Population pharmacokinetic analysis of mirtazapine

European Journal of Clinical Pharmacology volume 60, pages 473–480 (2004)Cite this article

Abstract

Objective

Mirtazapine belongs to the new generation of antidepressants that is commonly used in clinical routine. Therefore, we feel it mandatory to control compliance in the context of non-response, adverse events or other clinical situations by means of plasma concentration measurements. While controlled clinical studies have evaluated the effect of individual covariates on the pharmacokinetics of mirtazapine, our analysis aims to identify covariates within a naturalistic clinical setting.

Methods

We performed non-linear mixed-effects modelling with data from 65 depressed inpatients whose plasma concentrations were measured weekly during their stay in hospital. Each patient’s age, height, weight, co-medication, alcohol, coffee and cigarette consumption, weekly serum creatinine concentrations, liver enzyme activity, blood pressure and pulse was noted. From 49 patients, the genotype of cytochrome P 450 (CYP) isoenzymes 2D6, 2C9 and 2C19 was analysed.

Results

The clearance of CYP2D6 intermediate metabolisers was reduced by 26% compared with extensive metabolisers. No other factor significantly influenced the clearance of these patients.

Conclusion

The variability of mirtazapine plasma concentrations in clinical routine is caused to a relevant degree by CYP2D6. This should be taken into account when therapeutic drug monitoring is carried out to check treatment adherence or when a special clinical situation, such as co-morbidity and add-on medication, demands careful dosing of this drug.

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Acknowledgement

The study was supported by the “Kompetenznetz Depression/Suizidalität” of the German Ministry of Education and Research (BMBF).

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Affiliations

  1. Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53121 , Bonn, Germany

    Katja Grasmäder, Petra Louise Verwohlt, Kai-Uwe Kühn, Olrik von Widdern, Astrid Zobel, Marcella Rietschel, Wolfgang Maier & Marie Luise Rao

  2. Institute of Pharmacy, University of Bonn, An der Immenburg 4, 53121 , Bonn, Germany

    Ulrich Jaehde

  3. Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, 55131 , Mainz, Germany

    Aleksandra Dragicevic & Christoph Hiemke

Authors
  1. Katja Grasmäder
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  2. Petra Louise Verwohlt
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  3. Kai-Uwe Kühn
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  4. Aleksandra Dragicevic
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  5. Olrik von Widdern
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  6. Astrid Zobel
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  7. Christoph Hiemke
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  8. Marcella Rietschel
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  9. Wolfgang Maier
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  10. Ulrich Jaehde
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  11. Marie Luise Rao
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Correspondence to Marie Luise Rao.

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Grasmäder, K., Verwohlt, P.L., Kühn, KU. et al. Population pharmacokinetic analysis of mirtazapine. Eur J Clin Pharmacol 60, 473–480 (2004). https://doi.org/10.1007/s00228-004-0737-0

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  • DOI: https://doi.org/10.1007/s00228-004-0737-0

Keywords

  • Mirtazapine
  • Population pharmacokinetics
  • CYP2D6