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Therapeutic drug monitoring of clozapine and norclozapine in schizophrenia

N.V. Baymeeva1, L.M. Krasnykh1, V.G. Kaleda1, E.R. Nikolaeva1, S.A. Ivanova2, I.I. Miroshnichenko1
1 FSBI "Scientific center of mental health"
2 mental health research Institute Tomsk, NIMTS

Summary. The paper discusses are data of the therapeutic drug monitoring of clozapine received from 37 patients (98 samples in the whole), with various forms of schizophrenia undergoing treatment in the conditions of a hospital. The nature of dependence between concentration of clozapine, its metabolite of a norclozapine and a drug dose is established.

Materials and methods. The method of a high performance liquid chromatography with mass-spectrometric detection was developed for quantitative determination of clozapine and norclozapine in the blood. Monitoring with the subsequent analysis of data was accompanied with necessary clinical information, in the form of special forms of inquiry – the monitoring cards.

Results and discussion: The obtained data of clozapine level were distributed in the following way: 16 % were in the therapeutic, 51 % in sub-therapeutic (< 350 ng/mL) and 29 % conditionally toxic range (> 600 ng/mL), cases of alleged noncompliance did not exceed 3 %, in the appointment of clozapine at doses of 25 to 350 mg per day. Average concentrations of clozapine and norclozapine were higher in non-smoker than in smokers.

Сonclusion. Distribution on concentrations for clozapine and norсlozapine is substantially normal character, slightly offset towards larger values. Therapeutic drug monitoring is a necessary tool for the individualization and personalization of pharmacotherapy in the treatment of schizophrenia.

References: 
  • 1. Mosolov S.N., Tsukarzi E.E., Alfimov P.V. Algoritmy biologicheskoi terapii shizofrenii // Sovremennaya terapiya psi-khicheskikh rasstroistv. – 2014. – № 1. – S. 27–36.
  • 2. Hazari N., Kate N., Grover S. Clozapine and tardive movement disorders: a review // Asian journal of psychiatry. – 2013. – Vol. 6, No. 6. – P. 439–451.
  • 3. O’Connor D.W. et al. The safety and toler-ability of clozapine in aged patients: a retro-spective clinical file review // The World Journal of Biological Psychiatry. – 2010. – Vol. 11, No. 6. – P. 788–791.
  • 4. Miroshnichenko I.I. Ratsional'noe do-zirovanie i monitoring lekarstvennykh sredstv. – M.: Meditsinskoe informatsi-onnoe agentstvo, 2011. – 416 c.
  • 5. Dragovic S. et al. Characterization of hu-man cytochrome P450s involved in the bioac-tivation of clozapine //Drug Metabolism and Disposition. – 2013. – Vol. 41, No. 3. – P. 651–658.
  • 6. Ortiz de Montellano P.R. Cytochrome P450-activated prodrugs // Future medicinal chemistry. – 2013. – Vol. 5, No. 2. – P. 213–228.
  • 7. Baimeeva N.V., Bondarenko E.V., Pota-nin S.S., Miroshnichenko I.I. Koliche-stvennoe opredelenie soderzhaniya ari-piprazola, risperidona i ikh aktivnykh metabolitov v plazme krovi cheloveka po-sredstvom zhidkostnoi tandemnoi khroma-tomass-spektrometrii (VEZhKh/MS/MS) // Razrabotka i registratsiya lekarstvennykh sredstv. – 2014. – T. 8, № 3. – C. 32–37.
  • 8. Andrade C. Serotonin reuptake inhibitor treatment of obsessive-compulsive symptoms in clozapine-medicated schizophrenia // –2012. – Vol. 73, No. 11. – P. 1362–1364.
  • 9. Baimeeva N.V., Miroshnichenko I.I. Ana-lytical Methods for the Determination of Atypical Neuroleptics (Review) // Pharma-ceutical Chemistry Journal. – 2016. – Vol. 50, No. 5. – P. 339–345.
  • 10. Couchman L. et al. Plasma clozapine, norclozapine, and the clozapine: norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitor-ing service, 1993–2007 // Therapeutic drug monitoring. – 2010. – Vol. 32, No. 4. – P. 438–447.
  • 11. Ivanova S.A. et al. Cytochrome P450 1A2 co-determines neuroleptic load and may di-minish tardive dyskinesia by increased in-ducibility // The World Journal of Biological Psychiatry. – 2015. – Vol. 16, No. 3. – P.. 200–205.
  • 12. Barsegyan S.S., Maksimova T.V., Moro-zov Yu.E. Pletneva T.V., Salomatin E.M. , Tuchik E.S. Problemy ekspertnoi otsenki rezul'tatov sudebno-khimicheskikh issledo-vanii klozapina v biologicheskom materi-ale // Sudebno-meditsinskaya ekspertiza. – 2014. – № 5. – S. 40–46.
  • 13. Alfimov P.V., Oleneva E.V., Mosolov S.N. Prognosticheskie faktory terapev-ticheskoi effektivnosti klozapina pri shizofrenii [obzor literatury] // Sovre-mennaya terapiya psikhicheskikh rasstroistv. – 2013. – №. 2. – S. 21–29.