Association between CYP1A2 polymorphisms and clozapine-induced adverse reactions in patients with schizophrenia

We investigated the relationships between common polymorphisms in CYP1A2 (CYP1A2(⁎)1C and (⁎)1F), CYP1A2-mRNA levels in circulating lymphocytes and clozapine(CLZ)-induced adverse drug reactions (ADRs) in 34 patients. Patients with ADRs had a higher frequency of CYP1A2 low activity allele combinations (8/12; 67%) and lower CYP1A2-mRNA levels than patients without ADRs (6/22; 27%, P=0.019).

[1]  C. Eap,et al.  Nonresponse to Clozapine and Ultrarapid CYP1A2 Activity: Clinical Data and Analysis of CYP1A2 Gene , 2004, Journal of clinical psychopharmacology.

[2]  Magnus Ingelman-Sundberg,et al.  Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. , 2007, Pharmacology & therapeutics.

[3]  N. Poloni,et al.  Are CYP1A2*1F and *1C associated with clozapine tolerability? A preliminary investigation , 2011, Psychiatry Research.

[4]  Steven McGee,et al.  Simplifying likelihood ratios , 2002, Journal of General Internal Medicine.

[5]  J. van der Weide,et al.  The cytochrome P450 CYP1A2 genetic polymorphisms *1F and *1D do not affect clozapine clearance in a group of schizophrenic patients , 2005, Annals of clinical biochemistry.

[6]  G. Nappi,et al.  Two patients with COMT inhibitor–induced hepatic dysfunction and UGT1A9 genetic polymorphism , 2005, Neurology.

[7]  S. Preskorn,et al.  Examining Concentration-Dependent Toxicity of Clozapine: Role of Therapeutic Drug Monitoring , 2005, Journal of psychiatric practice.

[8]  J. Fourie,et al.  Treatment-Resistance to Clozapine in Association With Ultrarapid CYP1A2 Activity and the C → A Polymorphism in Intron 1 of the CYP1A2 Gene: Effect of Grapefruit Juice and Low-Dose Fluvoxamine , 2001, Journal of clinical psychopharmacology.

[9]  K. Holubar Two patients. , 2006, Journal of the American Academy of Dermatology.

[10]  P. Beaune,et al.  Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues , 2007, Pharmacogenetics and genomics.

[11]  B. Croissant,et al.  Reduction of side effects by combining clozapine with amisulpride: case report and short review of clozapine-induced hypersalivation-a case report. , 2005, Pharmacopsychiatry.

[12]  Paul D. Ellsworth,et al.  Diagnostic and Statistical Manual of Mental Disorder , 1980 .

[13]  M. Ingelman-Sundberg,et al.  Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. , 2007, Pharmacology & therapeutics.

[14]  R. Edwards,et al.  Interindividual Variation in Relative CYP1A2/3A4 Phenotype Influences Susceptibility of Clozapine Oxidation to Cytochrome P450-Specific Inhibition in Human Hepatic Microsomes , 2008, Drug Metabolism and Disposition.

[15]  J. Avorn,et al.  Pharmacogenetic Testing in the Clinical Management of Schizophrenia: A Decision-Analytic Model , 2005, Journal of clinical psychopharmacology.

[16]  K. Melkersson,et al.  Impact of CYP1A2 and CYP2D6 polymorphisms on drug metabolism and on insulin and lipid elevations and insulin resistance in clozapine-treated patients. , 2007, The Journal of clinical psychiatry.

[17]  Benveniste,et al.  Cytochrome P450 , 1993, Handbook of Experimental Pharmacology.

[18]  F. Harrell,et al.  Evaluating the yield of medical tests. , 1982, JAMA.

[19]  C. Eap,et al.  Increased Clozapine Plasma Concentrations and Side Effects Induced by Smoking Cessation in 2 CYP1A2 Genotyped Patients , 2005, Therapeutic drug monitoring.

[20]  H. Guchelaar,et al.  CYP1A2 activity is an important determinant of clozapine dosage in schizophrenic patients. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[21]  R. Bilder,et al.  Managing Treatment-Resistant Schizophrenia: Evidence from Randomized Clinical Trials , 2002, Journal of psychiatric practice.

[22]  T. Kamataki,et al.  Genetic polymorphism in the 5'-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. , 1999, Journal of biochemistry.