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We investigated clozapine (CLZ) tissue pharmacokinetics  in vivo  by using carbon‐11‐labeled CLZ ( 11 C‐CLZ) and positron emission tomography (PET). Eight healthy volunteers underwent  11 C‐CLZ studies wherein computed tomography image acquisition was followed by PET scans (whole‐body, four; brain, four). After bolus intravenous  11 C‐CLZ injection, PET images were acquired at various timepoints for 2–3 hours. Tissue  11 C‐CLZ signals were plotted over time, and pharmacokinetic parameters were determined. High  11 C‐CLZ radioactivity was detected in the liver and brain, implying CLZ hepatic metabolism and efficient blood–brain barrier penetration. The urinary and hepatobiliary tracts were involved in  11 C‐CLZ excretion. Moderate to high radioactivity was observed in the dopaminergic and serotonergic receptor‐rich brain regions, indicating CLZ binding to multiple receptor types. To our knowledge, this is the first study to report the determination of  11 C‐CLZ tissue pharmacokinetics in humans. PET using radiolabeled drugs can provide valuable information that could complement plasma pharmacokinetic data.

In Vivo Tissue Pharmacokinetics of Carbon‐11‐Labeled Clozapine in Healthy Volunteers: A Positron Emission Tomography Study