title: Albumin-binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac.
abstract: Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients. The binding of diclofenac to albumin was investigated in the aqueous humor. In a diclofenac binding assay with albumin in the aqueous humor of individual patients, diclofenac was extracted from aliquots of the aqueous humor, and its total levels were measured using ultra high performance liquid chromatography (UHPLC). Free diclofenac levels were measured using ultrafiltration and UHPLC. The albumin-binding fraction of diclofenac was 0.8 or higher in the aqueous humor of some patients. Ibuprofen significantly inhibited diclofenac binding to site II of albumin in mimic aqueous humor, but not in pooled aqueous humor. This difference may have been due to the weak binding of diclofenac to site II in the pooled aqueous humor. Flurbiprofen was used instead of diclofenac. Flurbiprofen has been shown to bind more strongly than diclofenac to the same site of albumin. Thus, the inhibitory effect of ibuprofen on the binding of flurbiprofen to albumin was investigated in pooled aqueous humor. The results indicated that ibuprofen significantly inhibited the flurbiprofen binding. An effective diclofenac administration method may be established for clinical application by the instillation of an appropriate inhibitor of binding to the albumin site II.
authors.affiliation: Department of Pharmacy University of Miyazaki Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki, Miyazaki, 889-1692, Japan; Ozaki Eye Hospital, 15 Kamezaki, Hyuga, 883-0066, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Osaki
authors.forename: Mineo
authors.initials: M
authors.lastname: Ozaki
authors.forename: Norito
authors.initials: N
authors.lastname: Takamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogata
authors.forename: Jin
authors.initials: J
authors.lastname: Tokunaga
authors.forename: Nao
authors.initials: N
authors.lastname: Setoguchi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arimori
mesh_terms: D060433:Administration, Ophthalmic; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001665:Binding Sites; D002386:Cataract / Q000378:metabolism*; D004008:Diclofenac / Q000493:pharmacokinetics*; D005480:Flurbiprofen / Q000493:pharmacokinetics; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012709:Serum Albumin; D004008:Diclofenac; D005480:Flurbiprofen; D007052:Ibuprofen
keywords: albumin; aqueous humor; cataract patient; diclofenac ophthalmic solution; protein binding