Experimental pharmacokinetics of the new neurotensine-derived antipsychotic drug dilept
Zherdev, V.P.; Boĭko, S.S.; Mesonzhnik, N.V.; Appolonova, S.A.; Rodchenkov, G.N.; Ostrovskaia, R.U.; Gudasheva, T.A.; Seredenin, S.B.
Eksperimental'naia i Klinicheskaia Farmakologiia 72(3): 16-21
2009
ISSN/ISBN: 0869-2092 PMID: 19642587 Document Number: 630680
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%.