[Experimental pharmacokinetics of the new neurotensine-derived antipsychotic drug dilept].
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%.
Zherdev
V P
VP
Boĭko
S S
SS
Mesonzhnik
N V
NV
Appolonova
S A
SA
Rodchenkov
G N
GN
Ostrovskaia
R U
RU
Gudasheva
T A
TA
Seredenin
S B
SB
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D013607:Tablets; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D014150:Antipsychotic Agents; C401484:GZR 123; D013607:Tablets; D014443:Tyrosine; D011392:Proline