Open AccessIn Vivo Tissue Pharmacokinetics of Carbon‐11‐Labeled Clozapine in Healthy Volunteers: A Positron Emission Tomography Study
Author(s) -
Park HS,
Kim E,
Moon BS,
Lim NH,
Lee BC,
Kim SE
Publication year - 2015
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.38
Subject(s) - pharmacokinetics , positron emission tomography , in vivo , medicine , pharmacology , nuclear medicine , biology , microbiology and biotechnology
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.