PET neuroimaging of [11C]mirtazapine enantiomers in pigs.
Previously, we used positron emission tomography (PET) for studying the pharmacokinetics of rac-[11C]mirtazapine in living brain. Our findings showed that rac-[11C]mirtazapine has suitable properties for PET neuroimaging. However, separate studies of enantiomers are typically required for characterizing the pharmacokinetics of a racemic drug. Therefore, we have determined the whole-body distribution and brain pharmacokinetics of S- and R-[11C]mirtazapine in pigs. The enantiomers of [11C]mirtazapine produced similar effective doses of radioactivity in most body organs, except for the brain, in which the dose was approximately 40% higher after injection of S-[11C]mirtazapine than the antipode. Kinetic analyses of dynamic brain PET recordings showed that values for regional accumulation of compound (k3) were significantly higher for S-[11C]mirtazapine than for the antipode, while the values for clearance of compounds from tissue to circulation (k2) were consistently lower for S-[11C]mirtazapine than for the R-form. No reliable difference occurred in the rate of metabolism of S- and R-[11C]mirtazapine in the bloodstream of the pigs. The present findings indicate that enantioselective processes affect the cerebral pharmacokinetics of rac-mirtazapine.
Smith
Donald F
DF
Center for Basic Psychiatric Research, Psychiatric Hospital of Aarhus University, 8240 Risskov, Denmark. dfsmith@inet.uni2.dk
Marthi
Katalin
K
Munk
Ole L
OL
Cumming
Paul
P
Hansen
Søren B
SB
Jakobsen
Steen
S
D000818:Animals; D001774:Blood Chemical Analysis; D001921:Brain / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes; D005260:Female; D007275:Injections, Intravenous; D007553:Isotope Labeling; D008803:Mianserin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000078785:Mirtazapine; D049268:Positron-Emission Tomography; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013552:Swine; D014915:Whole-Body Counting
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D008803:Mianserin; D000078785:Mirtazapine