Inefficient central nervous system delivery limits the use of ibuprofen in neurodegenerative diseases.
Chronic use of non-steroidal anti-inflammatory drugs may reduce the risk or delay the onset of Alzheimer's disease. To date, only limited information exists on the brain distribution of these drugs. The objective of this study was to determine the absolute brain delivery of ibuprofen by using constant in vivo infusion in rats. Ibuprofen was infused to steady-state concentrations both in plasma and brain tissue. Ibuprofen levels in plasma and brain tissue were measured by RP-HPLC after the plasma and the brain samples were purified by protein precipitation and solid phase extraction, respectively. Results indicate that both plasma and brain concentrations reached steady-state within 6h, and that the brain to plasma ratio of ibuprofen was only 0.02. Thus, limited brain penetration prevents the possible use of ibuprofen in treating or preventing neurodegenerative disorders such as Alzheimer's disease.
Mannila
Anne
A
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. anne.mannila@uku.fi
Rautio
Jarkko
J
Lehtonen
Marko
M
Järvinen
Tomi
T
Savolainen
Jouko
J
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D007052:Ibuprofen / Q000008:administration & dosage* / Q000378:metabolism*; D008297:Male; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007052:Ibuprofen