Comparative kinetics of oxiracetam in serum and CSF of patients with dementia of Alzheimer type.
The purpose of the study was to determine whether oxiracetam crosses the human blood-brain barrier and to evaluate its comparative kinetics in serum and in cerebro-spinal fluid (CSF). Six DAT patients, undergoing CSF collection for diagnostic purposes, received 2 g oxiracetam daily, by a 60 min i.v. infusion, for 7 days. On the last day, in four patients blood samples were collected at time 0, 30, 60 and 120 min, and lumbar drainage was performed at the end of infusion: at this time mean CSF concentration was 3.5 micrograms/ml, i.e. 4.0% of the serum one, demonstrating that oxiracetam crosses the blood-brain barrier. In two patients, blood samples were collected at time 0, 60, 120 and 240 min, and lumbar drainage was performed 60 min after the end of infusion: at this time mean CSF concentration was 2.8 micrograms/ml, i.e. 5.3% of the serum one, indicating a persistence of oxiracetam within this deep compartment. These results provide the first evidence in humans that oxiracetam penetrates the central nervous system and contribute to the understanding of its long-lasting pharmacodynamic effect in man.
Parnetti
L
L
Chair of Gerontology and Geriatrics, Perugia University, Italy.
Mecocci
P
P
Gaiti
A
A
Cadini
D
D
Lombardi
F
F
Visconti
M
M
Senin
U
U
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011759:Pyrrolidines / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
D001798:Blood Proteins; D002556:Cerebrospinal Fluid Proteins; D011759:Pyrrolidines; C040619:oxiracetam