Permeability of the Blood-Brain Barrier for Dilept and Its Active Metabolite

• Published in: Bulletin of experimental biology and medicine 2011-07, Vol.151 (3), p.330-332
• Main Authors: Zherdev, V. P., Boyko, S. S., Mesonzhnik, N. V., Bastrygin, D. V.
• Format: Article
• Language: English
• Subjects: Animals; Antipsychotic Agents - metabolism; Antipsychotic Agents - pharmacokinetics; Biological Transport; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain; Brain - blood supply; Brain - metabolism; Cell Biology; Chromatography, High Pressure Liquid; Diffusion; Drugs; Internal Medicine; Laboratory Medicine; Male; Membrane permeability; Metabolites; Neuroleptics; Pathology; Peptides; Permeability; Pharmacology and Toxicology; Proline - analogs & derivatives; Proline - metabolism; Proline - pharmacokinetics; Rats; Tandem Mass Spectrometry; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Tyrosine - pharmacokinetics
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-011-1322-z

Experiments on rats with measurements by HPLC-MS/MS showed that antipsychotic preparation dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) administered per os in doses of 40 and 200 mg/kg crossed the blood-brain barrier and was detected in rat brain (unchanged drug and its active metabolite N-caproyl-L-prolyl-L-tyrosine). The brain/plasma distribution coefficient for dilept was 2.0, for metabolite 0.5. No dose-concentration relationship was found, presumably because of the high dose of the drug transported from the blood to the brain not only by free diffusion, but also with participation of active carriers, whose number was limited.