Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole

Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole

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.

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