Synthesis, pharmacokinetics, and pharmacodynamics studies of valsartan peptide derivatives

Abstract

In order to increase the intestinal permeability of valsartan, 14 esters and peptide derivatives of valsartan were chemically synthesized and their absorption characteristics were described. All derivatives were stable and could be better absorbed into the small intestine than valsartan. There are two barriers for the absorption of valsartan derivatives. The elongated half-life (t(1/2)) and stable blood concentrations for compound 4 due to the hydrolysis of the ester group in the second barrier were demonstrated in pharmacokinetic experiments. Furthermore, compound 4 also displayed modest anti-hypertension activity in vivo, which makes structural modification of valsartan, especially for the purpose of improvement of its intestinal permeability, valuable for further studies.