Clozapine, CYP1A2 Polymorphism, CYP2C19 Polymorphism, Schizophrenia
Conditions
Brief summary
Clozapine (Clz), an atypical antipsychotic, is the reference medication for patients with treatment-resistant schizophrenia. Due to the high inter-individual variability of its pharmacokinetics and its narrow therapeutic index, a close therapeutic drug monitoring (TDM) of Clz is highly recommended. Several factors can cause a variation in the pharmacokinetics as age, smoking habits, coffee consumption and drug interaction. Genetic factors related to hepatic expression levels of the cytochrome P450 (CYP), regulate the hepatic clearance of Clz, thereby determine its bioavailability. The CYP1A2 and CYP2C19 isoenzymes are mainly responsible for the metabolism of several drugs including Clz. It has been demonstrated that there is an interethnic variation in the expression and function of these two isoenzymes. This variation is caused by single nucleotide polymorphisms (SNPs) of genes encoding these proteins. While the Influence of the different polymorphisms related to CYP1A2 and CYP2C19 have been established especially in Asian and Caucasian populations, no study has examined the impact of these SNPs in the southern Mediterranean populations. Moreover, the impact of these SNPs is very controversial. The present study aims to investigate in Tunisian schizophrenic patients, the influence of genetic (CYP1A2 and CYP2C19 polymorphisms) and non-genetic factors on Clz pharmacokinetics.
Interventions
OTHERDetermination of plasma concentration of clozapine/ Genotyping
Determination of trough plasma concentration of clozapine (C0) Genotyping of CYP1A2 & CYP2C19
Sponsors
University of Monastir
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Schizophrenic patients receiving clozapine * Good adherence to the treatment (clozapine)
Exclusion criteria
* Patients who were co-prescribed drugs that affected the pharmacokinetics of Clozapine. * Patients who presented gastrointestinal disorders disturbing absorption of clozapine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of trough plasma concentration of clozapine (C0) | One and a half months | Technique : HPLC/UV (high-performance liquid chromatography associated with a UV detector) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the correlation between the presence of CYP1A2*1F (rs762551;-163C> A), CYP1A2*1C (rs2069514;-3860 G> A) and CYP 2C19*2 (rs4244285; 681G>A) and the variability of C0/Daily dose. | One and a half months | \- Technique: PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) |
Countries
Tunisia
Outcome results
None listed