PubMed · 9700301
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A Ostins. 1998. Post-operative fluids.. https://doi.org/10.1177/004947559802800333
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Trimetazidine (TMZ), an anti-ischemic agent with proposed antioxidant properties, was used in a chronic colitis model in order to evaluate its effectiveness as a therapeutic agent in chronic colitis. Treatment of male Swiss Albino rats with ethanol (50%) and trinitrobenzenesulfonic acid (TNBS) (30 mg/kg) produced colitis as evidenced by histopathologic damage and inflammatory alterations, lipid peroxidation [increased malondialdehyde (MDA) levels], and enhanced neutrophil infiltration [increased myeloperoxidase (MPO) activity] without marked change in glutathione status. Administration of TMZ (5 mg/kg) to TNBS-treated rats failed to affect the TNBS-induced changes in histopathology and MPO activities. Unexpectedly, intrarectal (i.r.) administration of TMZ significantly elevated colonic MDA levels to a greater extent than TNBS alone. Intraperitoneal (i.p.) TMZ treatment seemed to increase total glutathione (tGSH), GSH, and GSH/GSSG values. In conclusion, our results demonstrated that (a) i.r. administration of ethanol and TNBS is an effective way of inducing a chronic colitis model, (b) inflammation and lipid peroxidation augment tissue damage in the chronic colitis model, (c) i.p. TMZ treatment significantly inhibits MDA production in the chronic colitis model, (d) TMZ treatment is more effective via the i.p. compared to i.r. route, and (e) TMZ seems to show its antioxidant effect via preserving the tissue's GSH/GSSG ratios.
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The investigated drug delivery system is a solid-reversed-micellar-solution (SRMS). The composition of this solution is 70% Witepsol W35 and 30% (w/w) lecithin. 1% (w/w) metoclopramide-HCl (MCP) was solubilized in the SRMS. After melting and on contact with water or any physicological aqueous media the SRMS exhibits an application induced transformation into a semisolid system of liquid crystalline microstructure. The structure of the liquid crystal has been identified by polarized light microscopy as a lamellar mesophase. Due to a low coefficient of diffusion in this mesophase a controlled release of the drug may be possible. The release profiles of the in vitro experiments have shown zero order kinetics and a sustained release of the SRMS-suppositories (SRMS-supp.) in comparison with commercial suppositories (Gastrosil-supp.). To examine bioavailability an in vivo study with rabbits was carried out. Five SRMS-supp. (10 mg MCP) and five Gastrosil-supp. (10 mg MCP) were tested in a parallel-group study. These experiments have shown a five times longer mean residence time (parameter of sustained release) in comparison with Gastrosil-supp. In vitro and in vivo studies have shown that rectal application of SRMS-supp. provides an appropriate route for controlled release of MCP via application induced transformation into liquid crystals.