生物活性

• 描述Diflunisal, a nonsteroidal anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro. Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life^[3]. Diflunisal exhibits activity after oral administration with potency about 25 times greater than that of aspirin, about 3 times that of glafenine and twice that of zomepirac. Repeated administration of large doses produced neither tolerance nor sensitization to the analgesic action of diflunisal^[4]. Administration of increasing doses of diflunisal to rats shows that the effect of the dose on the pharmacokinetics of diflunisal is quite complicated. The CLp is reduced considerably when the dose increases from 3 to 10 mg/kg and then remains relatively constant over the dose range of 10 to 60 mg/kg. Diflunisal has been shown to be highly bound to rat plasma protein and dependent on concentration. The fraction of unbound diflunisal is increased about 10-fold over the concentration range of 5 to 300 μg/mL^[5]. Diflunisal, an aspirin-like nonsteroidal anti-inflammatory drug (NSAID), specifically inhibits in vitro and in vivo the chemotactic activity of HMGB1 at nanomolar concentrations, at least in part by binding directly to both HMGB1 and CXCL12 and disrupting their heterocomplex^[6].