%0 Journal Article
%T Pharmacokinetics and tissue distribution study of two novel quinazoline PI3K/mTOR dual-inhibitors, potential anticancer agents.
%A Chen J
%A Bian X
%A Zhang S
%A Yang G
%J Pak J Pharm Sci
%V 36
%N 5
%D 2023 Sep
%M 37869929
%F 0.863
%X S1 and S2, two structurally similar quinazoline derivatives, are novel anticancer drugs targeting the PI3K/AKT/mTOR signaling pathway channel. However, their pharmacokinetic and tissue distribution characteristics are unknown, which has hindered further development and in-depth studies. In this study, a simple, rapid and sensitive method using high performance liquid chromatography was established and validated to quantitatively study the pharmacokinetics and tissue distribution profiles of S1 and S2 in rats following intravenous injection. The results indicated that after intravenous injection, the elimination of S1 and S2 fit the two-compartment model and linear pharmacokinetics characteristics were observed. Furthermore, S1 and S2 were widely distributed and found in high concentrations in liver and kidney tissues and a small proportion of S1 and S2 could cross the blood-brain barrier and be distributed in the brain. The current findings will contribute to interpretation and understanding the relationship between dosage and pharmacodynamic effects of S1 and S2.