The study of intestinal absorption and biodistribution in vivo of proton pump inhibitors was written by Shen, Tianxiang;Jiang, Xindong;Jin, Zhaolei;Ji, Qiuzhi;Li, Chunlong;Li, Qingpo;Long, Hongxin;Qiu, Weigen;Wang, Wei;Hou, Xuemei;You, Jian. And the article was included in European Journal of Pharmaceutics and Biopharmaceutics in 2020.Electric Literature of C18H20N3NaO3S The following contents are mentioned in the article:
The major therapeutic strategy for acid-related gastrointestinal diseases in clinic is to reduce the excretion of gastric acid by oral administration of proton-pump inhibitors (PPIs). However, it is quite a challenge to study the oral absorption behaviors of PPIs considering their extreme instability under gastrointestinal environment. As a result, little information has been reported on PPI oral absorption so far, hindering the further development of PPI-contained oral preparations Here, we first investigated the degradation rate of three representative PPIs, including ilaprazole, ilaprazole sodium and rabeprazole sodium. Then a modified in situ intestine absorption method in rat was established: through the temperature control by the heat exchangers, the perfusate was kept at physiol. temperature only when passing through the intestine while it was maintained at 4°C outside the intestine. Therefore PPIs could maintained sufficiently high stability under proper temperature control. Our data demonstrated that both ilaprazole and ilaprazole sodium exhibited significantly higher absorption efficiency than rabeprazole sodium did through the comparison of their apparent permeability coefficients and steady-state plasma concentrations after perfusion in the duodenum, jejunum, ileum and colon, mainly attributing to their more suitable oil-water partition coefficient The duodenum could be the best site for the oral absorption of PPIs. Ilaprazole outperformed its sodium salt form with its stable absorption behavior in tested four intestinal segments. Furthermore, after i.v. or oral administration, ilaprazole exhibited a longer residence time and a higher accumulation in the stomach than in most of other tissues/organs. However, it was also found that the accumulation was heterogeneous and mainly located in mucosa cells of the stomach. Our further study indicated that there was no significant difference on the oral absorption efficiency of ilaprazole between female and male rats but ilaprazole underwent a faster metabolism in male rats after oral absorption. Our study provided a valuable guidance for the design of oral formulation and the optimization of PPI-contained formulations. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Electric Literature of C18H20N3NaO3S).
Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. The pharmacophore of imidazole exists in bioactive compounds including amino acids, plant growth regulators and therapeutic agents.n increase of the alkyl chain length of the alcohols. Electric Literature of C18H20N3NaO3S
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem