Autor: |
Vp, Zherdev, Ss, Boĭko, Nv, Mesonzhnik, Sa, Appolonova, Gn, Rodchenkov, Ru, Ostrovskaia, Tatiana Gudasheva, Sb, Seredenin |
Rok vydání: |
2009 |
Předmět: |
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Zdroj: |
Europe PubMed Central |
ISSN: |
0869-2092 |
Popis: |
The metabolism and pharmacokinetics of a new neurotensine-derived dipeptide drug dilept (N-caproyl-L-prolyltyrosine methyl ester) and its tentative metabolites after intravenous and peroral administration of the parent drug and its tabletized form in rats have been studied by HPLC-ESI(-)-MS/MS method. It is established that unchanged dilept (detected in the blood plasma for no less than 30 min) as well as N-caproyl-L-proline and N-caproyl-L-prolyl-L-tyrosine (both detected in the blood over more than 4 h) are the major metabolites in the bloodstream upon peroral administration of the drug. The proposed structures of metabolites were confirmed by countersynthesis. Dilept and N-caproyl-L-prolyl-L-tyrosine penetrate through the blood - brain barrier. The drug is rapidly absorbed, distributed, and metabolized in the rat organism. Peroral administration of dilept in rats in the form of tablets (at a dose of 200 mg/kg) resulted in a significant increase in intestinal absorption, as evidenced by a 22% improvement in the bioavailability, whereas dilept alone showed an absolute bioavailability of less than 1%. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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