title: Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin.
abstract: OBJECTIVE
  The aim of the present study was investigating the effects of three anti-inflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined.
  
  
  METHODS
  Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrations were measured by HPLC. Finally, Sirolimus protein binding parameters was calculated using Scatchard plots. The same processes were conducted in the presence of NSAIDs at lower concentration of albumin and different pH conditions. To characterize the binding site of Sirolimus on albumin, the free concentration of warfarin sodium and Diazepam, site I and II specific probes, bound to albumin were measured upon the addition of increasing Sirolimus concentrations.
  
  
  RESULTS
  Based on the obtained results presence of Diclofenac, Piroxicam and Naproxen, could significantly decrease the percentage of Sirolimus protein binding. The Binding reduction was the most in the presence of Piroxicam. Sirolimus-NSAIDs interactions were increased in higher pH values and also in lower albumin concentrations. Probe displacement study showed that Sirolimus may mainly bind to site I on albumin molecule.
  
  
  CONCLUSIONS
  More considerations in co-administration of NSAIDs and Sirolimus is recommended.
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Arash
authors.initials: A
authors.lastname: Khodaei
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Soheila
authors.initials: S
authors.lastname: Bolandnazar
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
authors.affiliation: Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences, Zanjan, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Hasani
authors.affiliation: Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Zakeri-Milani
keywords: NSAIDs; Protein binding; Sirolimus; Site I; Site II; Ultrafiltration