[Human positron emission tomography with oral 11C-vinpocetine].
BACKGROUND
Positron emission tomography (PET) is a useful tool for the investigation of certain physiological changes and for the evaluation of the distribution, and receptor binding of drugs labelled with positron emitting isotopes. Vinpocetine (ethyl-apovincaminate) is a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases. In the clinical practice vinpocetine is usually administered to the patients in intravenous infusion followed by long-term oral treatment. Until presently human data describing vinpocetine's kinetics and brain distribution came from ex vivo (blood, plasma, liquor) and post mortem (brain autoradiography) measurements.


OBJECTIVE
The authors wished to investigate the kinetics and distribution of vinpocetine in the brain and body after oral administration with PET in order to prove, that PET is useful in the non-invasive in vivo determination of these parameters.


METHODS
Vinpocetine was labelled with carbon-11 and the radioactivity was measured by PET in the stomach, liver, brain, colon and kidneys in healthy male volunteers. The radioactivity in the blood and urine was also determined.


RESULTS
After oral administration, [11C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the oral administration of the labelled drug (average maximum uptake: 0.7% of the administered total dose). Brain distribution was heterogeneous (with preferences in the thalamus, basal ganglia and occipital cortex), similar to the distribution previously reported by the authors after intravenous administration.


CONCLUSIONS
Vinpocetine, administered orally to human volunteers, readily entered the bloodstream from the stomach and the gastrointestinal tract and thereafter passed the blood-brain barrier and entered the brain. Radioactivity from [11C]vinpocetine was also demonstrated in the kidneys and in urine. The study demonstrates that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally administered labelled drugs active in the central nervous system in the living human body.
Vas
Adám
A
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Stockholm.
Christer
Halldin
H
Sóvágó
Judit
J
Johan
Sandell
S
Cselényi
Zsolt
Z
Kiss
Béla
B
Kárpáti
Egon
E
Lars
Farde
F
Gulyás
Balázs
B
D000284:Administration, Oral; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000008:administration & dosage; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012016:Reference Values; D013997:Time Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014748:Vinca Alkaloids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D002250:Carbon Radioisotopes; D018696:Neuroprotective Agents; D014748:Vinca Alkaloids; C013983:vinpocetine