Background: Tolmetin (Tol) is a pyrrole acetic acid derivative that acts as a highly effective topical anti-inflammatory agent. Topical administration of Tol is effective for the management of ocular inflammations.The aim of this study was to formulate and improve a topical ophthalmic delivery system of Tol. Materials and methods: In the present study, ocular inserts of Tol were prepared using ...

Background: Tolmetin (Tol) is a pyrrole acetic acid derivative that acts as a highly effective topical anti-inflammatory agent. Topical administration of Tol is effective for the management of ocular inflammations.The aim of this study was to formulate and improve a topical ophthalmic delivery system of Tol. Materials and methods: In the present study, ocular inserts of Tol were prepared using ...

Although zomepirac (ZP) and tolmetin (TM) induce anaphylactic reactions and form reactive acyl glucuronides, a direct link between the two events remains obscure. We report herein that, in addition to acyl glucuronidation, both drugs are subject to oxidative bioactivation. Following incubations of ZP with human liver microsomes fortified with NADPH and glutathione (GSH), a metabolite with an MH...

The chemical reactivity of acyl glucuronide (AG) has been thought to be associated with the toxic properties of drugs containing carboxylic acid moieties, but there has been no direct evidence showing that AG formation is related to the observed toxicity. In the present study, the cytotoxicity of AGs, especially that associated with the inflammatory response, was investigated. The changes in th...

The chemical reactivity of acyl glucuronide (AG) has been thought to be associated with the toxic properties of drugs containing carboxylic acid moieties, but there has been no direct evidence showing that AG formation is related to the observed toxicity. In the present study, the cytotoxicity of AGs, especially that associated with the inflammatory response, was investigated. The changes in th...

In situ drug and organic electrolyte complex tablets were investigated as extended release dosage forms. Incorporating a 1:1 molar ratio of diltiazem HCl and an anionic organic electrolyte (i.e., Na deoxycholate) into HPC tablets extended the total release time with a near zero – order release rate (release exponent, n = 0.85 – 0.97) due to in situ complex formation of the drug and the organic ...

Acylglucuronides formed from carboxylic acids by UDP-glucuronosyltransferases (UGTs) are electrophilic metabolites able to covalently bind proteins. In this study, we demonstrate the reactivity of the acylglucuronide from the nonsteroidal antiinflammatory drug, ketoprofen, toward human and rat liver UGTs. Ketoprofen acylglucuronide irreversibly inhibited the glucuronidation of 1-naphthol and 2-...