Enhanced bioavailability of a new thiazolidine derivative FPFS-410, an antidiabetic and lipid-lowering drug, after oral administration of its hydroxypropyl-β-cyclodextrin complex to bile duct-cannulated rats

Application of ultrasound‐guided cholecystocentesis to the evaluation of the metabolite profiling in bile of dogs and cynomolgus monkeys

“…The reason for this difference is unknown but may indicate differences in enzyme or transporter levels between the intact (UCC) and BDC animals. Such differences between intact and BDC animals have been noted in the literature and may be a result of inflammation in the BDC monkeys . Another potential source of minor differences between the UCC and BDC profiles is the sedative administered at 4‐6 hours and again at 24 hours prior to the cholecystocentesis.…”

“…It is unclear what may be the cause of this difference in relative levels of glucuronide and parent in bile, although there are published precedents for differences in the metabolism and disposition of compounds in bile duct cannulated animals compared to intact animals. These differences have been variously attributed to changes in absorption, decreases/increases in metabolic enzymes and transporters, and changes in gut microflora . Propofol administration may also have an unknown impact on the metabolite profile at 24 hours in the UCC dogs, although it should have minimal impact on the 6 hours sample.…”

“…From a scientific perspective, bile samples obtained through UCC in intact animals avoid potential complications of an altered drug metabolism and disposition profile that has been noted for some compounds in BDC animals and which may impact interpretation of the relative contributions of clearance routes. Moreover, the bile sample collection is well controlled with UCC.…”

“…This requires separate space and animal maintenance. Furthermore there are publications indicating that bile duct‐cannulation itself can affect the metabolism and disposition of a drug candidate, which may lead to erroneous conclusions and predictions of clinical metabolism and disposition …”

The Influence of Cosolvent on the Complexation of HP-β-cyclodextrins with Oleanolic Acid and Ursolic Acid

“…This can result in improved chemical stability, an increase in the apparent aqueous solubility, and higher bioavailability without changing their pharmacokinetic properties (4)(5)(6)(7)(8). CDs have mainly been used as complexing agents in the pharmaceutical industry to increase aqueous solubility of poorly water-soluble drugs (9,10).…”