Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics

University of Monastir

Status: Completed

Conditions: CYP1A2 Polymorphism; Schizophrenia; Clozapine; CYP2C19 Polymorphism

Treatments: Other: Determination of plasma concentration of clozapine/ Genotyping

Study type: Interventional

Funder types: Other

Identifiers

NCT04240496

IORG 0009738 N°30

Details and patient eligibility

About

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.

Enrollment: 51 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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51 participants in 1 patient group

Schizophrenic patients

Other group

Description:

* Determination of trough plasma concentration of clozapine (C0) * Genotyping of CYP1A2 \& CYP2C19 Drug: Leponex (Clozapine) : was started at a dose of 25 mg/j, the dose was gradually increased and was administered in one, two or three divided doses.

Treatment:

Other: Determination of plasma concentration of clozapine/ Genotyping