Investigation of the pharmacokinetics and metabolic fate of Fasiglifam (TAK-875) in male and female rats following oral and intravenous administration

Minimizing the DILI potential of carboxylic acid-containing drugs: a perspective

“…In addition, as can be seen from Fig. 3, based on the circulating metabolites of fasiglifam detected in the rat, a large range of biotransformations were seen [18,19].…”

“…For ethanoic acids, such as e.g., diclofenac, a reaction first observed in vitro by Grillo et al results ultimately, via the loss of the linking CH 2 , in the oxidative decarboxylation of the drug and side chain shortening to a benzoate structure [59]. This reaction was also seen in vivo in the rat [60] and has more recently been observed for the withdrawn NSAIDs lumiracoxib [61] and fenclozic acid [62] and recently, the antidiabetic drug fasiglifam [18].…”

“…3 The circulating metabolites of fasiglifam (TAK875), shown as semi-localized structures indicating the likely sites of metabolism where these could not be determined with confidence based on MSMS data alone (ref. [18] with permission) conjugates [29]. When applied to a number of NSAIDs a correlation between the rate of formation of the cysteine adduct from the conjugates, the drugs' AUC and DILI was obtained.…”

Orally-administered nanomedicine systems targeting colon inflammation for the treatment of inflammatory bowel disease: latest advances

“…Furthermore, it eliminates the need for drugs to pass through the stomach, removing the influence of the gastric environment on drug delivery design and creating more research opportunities for drug retention rates. 17,18 However, injection administration requires professional personnel and specialized equipment, and patients often experience pain, which may lead to resistance. Additionally, injection administration can have significant systemic side effects due to its high efficiency compared to other administration routes.…”