Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole

Universiti Sains Malaysia33 enrolled

Overview

Clozapine is an effective treatment for patients with schizophrenia who do not respond to other therapies, but its blood concentration varies widely between individuals due to genetic and physiological differences. Proton pump inhibitors such as pantoprazole are often prescribed in this population to prevent stomach discomfort, yet their impact on clozapine exposure has not been fully characterized. This clinical study will investigate the pharmacokinetics of clozapine and its main metabolite norclozapine, the influence of individual characteristics on drug exposure, and the effect of pantoprazole coadministration. Healthy adult volunteers will participate in a randomized open label cross over design, receiving a single dose of clozapine alone and again after pantoprazole treatment. Outcomes include clozapine and norclozapine plasma concentration time profiles, pharmacokinetic parameters, and safety assessments.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy Volunteers - Male and Female

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Healthy adult volunteers aged 18 to 50 years 2. No history of chronic medical or psychiatric disease, as confirmed by baseline medical evaluation, medical history, and electrocardiogram (ECG) 3. No use of any medications for at least two weeks before study initiation Exclusion Criteria: 1. Pregnant or breastfeeding women 2. Current smokers

Outcomes

Primary Outcomes

Peak Plasma Concentration (Cmax)

Maximum plasma concentration of clozapine following a single oral dose

Time frame: From pre-dose to 8 hours after a single oral dose of clozapine

Area Under the Plasma Concentration-Time Curve (AUC)

AUC of clozapine plasma concentration from time zero to the last measurable concentration following a single oral dose

Time frame: From pre-dose to 8 hours after dosing

Secondary Outcomes

Area Under the Concentration-Time Curve Extrapolated to Infinity (AUCinf)

Area under the plasma concentration-time curve from time zero extrapolated to infinity

Time frame: From pre-dose to last measurable concentration

Time to Peak Concentration (Tmax)

Time to reach maximum observed plasma concentration of clozapine