Influence of Endogenous Substances on Site-II to Site-I Displacement of Diclofenac Bound to Albumin in the Aqueous Humor of Patients with Cataract

Biol Pharm Bull. 2023 Dec 7. doi: 10.1248/bpb.b23-00301. Online ahead of print.ABSTRACTDiclofenac instillation is useful in preventing intraoperative miosis and macular edema caused by postoperative inflammation in cataract surgery; however, optimum efficacy is not attained when the instilled diclofenac strongly binds to albumin in patients' aqueous humor. Therefore, a method that inhibits diclofenac binding and increases the concentration of its free fraction is needed. We conducted a basic study regarding the effects of inhibitors on the binding of instilled diclofenac to albumin and endogenous substances in aqueous humor. Aqueous humor samples from 16 patients were pooled together for analysis. The free fraction of diclofenac was measured using ultrafiltration methods in various experiments with pooled and mimic aqueous humor. Free fraction of diclofenac, a site II drug, in pooled aqueous humor was 0.363 ± 0.013. The binding of diclofenac in the presence of phenylbutazone (PB), a site I inhibitor, was significantly inhibited (free fraction = 0.496 ± 0.013); however, no significant inhibition by ibuprofen, a site II inhibitor, (free fraction = 0.379 ± 0.004), was observed. The unexpected result was due to free fatty acids [FFAs; palmitic acid (PA)] and tryptophan (L-Trp). The inhibition of diclofenac binding by PB in the mimic aqueous humor containing these endogenous substances revealed significant binding inhibition in the presence of PA and L-Trp. Diclofenac is strong...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Source Type: research