Monitoring of clozapine and norclozapine concentrations in schizophrenia treatment
Abstract
The article discusses therapeutic drug monitoring (TDM) data for clozapine obtained in patients with various forms of schizophrenia undergoing treatment in hospital. Clozapine and its metabolite norclozapine concentrations and their response to the administered drug doses have been studied. Clozapine and norclozapine assay in human blood has been performed by high performance liquid chromatography with mass spectrometric detection. Monitoring and subsequent data analysis has been supported with necessary clinical information in the form of special requests - TDM cards. The obtained data on concentration levels have been arranged as follows: 38.64 % within therapeutic range, 38.64 % within subtherapeutic range (<350 ng/ml) and 22.73 % within arbitrary toxic range (600 ng/ml) when administering 25 to 30 mg of clozapine daily. Average concentrations of clozapine and norclozapine were higher in non-smokers compared to smokers.
About the Authors
N. V. Baymeeva
Scientific Center of Mental Health
Russian Federation
Russian Federation
L. M. Krasnykh
Scientific Centre for Expert Evaluation of Medicinal Products
Russian Federation
Russian Federation
I. I. Miroshnichenko
Scientific Center of Mental Health
Russian Federation
Russian Federation
References
1. Hazari N, Kate N, Grover S. Clozapine and tar dive movement disorders: a review. Asian J Psychiatr. 2013; (6): 439–51.
2. O’Connor DW, Sierakowski C, Fei Chin L, Singh D. The safety and tolerability of clozapine in aged patients: A retrospective clinical file review. World J Biol Psychiatry 2010; (11): 788–91.
3. Miroshnichenko II. Rational dosing and monitoring of medicines. Moscow: Meditsinskoe informatsionnoe agentstvo; 2011 (in Russian).
4. Dragovic S, Gunness P, Ingelman-Sundberg M, Vermeulen NPE, Jan NM. Commandeur characterization of human cytochrome P450s involved in the bioactivation of clozapine. Drug Metab Dispos. 2013; 41: 651–8.
5. Rodina TA, Melnikov ES, Sokolov AV, Belkov SV, Ramenskaya GV. Definition of enalapril and enalaprilat, the active metabolite in the blood plasma by HPLC-MS/MS in the personalization of pharmacotherapy of patients with hypertension. Eksperimentalnaya i klinicheskaya farmakologiya 2015; 78(10): 15–20 (in Russian).
6. Baymeeva NV, Bondarenko EV, Potanin SS, Miroshnichenko II. Quantitative determination of aripiprazole, risperidone and its active metabolites in human plasma by liquid chromatography tandem-mass spectrometry (HPLC/MS/MS). Razrabotka i registratsiya lekarstvennyh sredstv 2014; 3(8): 32–7 (in Russian).
7. Krasnykh LM, Platova AI, Baymeeva NV, Vasilenko GF. Measurement of clozapine and norclozapine in blood plasma by tandem mass spectrometry. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya 2014; (1): 37–41 (in Russian).
8. Couchman L, Morgan PE, Spencer EP, Flanagan RJ. Plasma clozapine, norclozapine, and the clozapine:norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service 1993–2007. Ther Drug Monit. 2010; 32(4): 438–47.
Review
For citations:
Baymeeva N.V., Krasnykh L.M., Miroshnichenko I.I. Monitoring of clozapine and norclozapine concentrations in schizophrenia treatment. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2016;(4):53-57. (In Russ.)
Views:
641
Email this article 