Bendazac Lysine

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Abstract
Bendazac is an oxyacetic acid with anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties, but its principal effect is to inhibit the denaturation of proteins. The lysine salt, which is better absorbed than the parent compound after oral administration, has been evaluated as a treatment for cataract, a condition which appears to result mainly from the denaturation, aggregation and precipitation of proteins within the lens. Results from a very small number of preliminary studies using objective photographic and densitometric methods have suggested that oral bendazac lysine, usually at a dosage of 500mg 3 times daily, can stabilise the progression of lens opaciflcation in patients with cataract. Significant improvements in individual and mean visual acuities in treated patients have been reported by several studies, but this parameter is not universally accepted as a reliable index of lens status. Preliminary studies evaluating bendazac lysine 0.5% eyedrops have reported comparable results to those obtained with oral treatment. Overall, tolerability of the drug has been good in studies to date. A dose-related laxative effect and other gastrointestinal disturbances are the most common adverse effects associated with oral therapy, and a transient burning sensation is the most commonly reported symptom occurring with eyedrop application. Bendazac lysine is one of a number of agents which have been introduced for the management of cataract. Although the results of preliminary studies have suggested that the drug may be useful for delaying the progression of cataract, further clinical studies using proven objective methods are required to fully establish its value in the management of this condition and its long term tolerability. The principal action of bendazac is an antidenaturant effect on protein. The drug has been shown in vitro to inhibit denaturation of various types of protein, including bovine serum albumin, serum and crystalline lens proteins by heat, ultraviolet radiation, free radicals and chemicals. In vivo protection of lens proteins has also been demonstrated in animals administered the drug orally as the lysine salt. Apparent improvement of the blood-retinal barrier has been observed in a preliminary study involving diabetic patients treated with bendazac lysine 500mg 3 times daily for 3 to 6 months. Topical bendazac has demonstrated anti-inflammatory activity in animal models and in clinical studies, and has proved effective in the treatment of various dermatoses, particularly those with a necrotic component. The drug also has choleretic and antilipidaemic effects. Significant reductions in total lipid, total cholesterol and triglyceride levels and beta/alpha lipoprotein ratio have been reported in patients with dyslipidaemia receiving oral bendazac lysine 500mg 3 times daily. Bendazac has also been shown to inhibit phytohaemagglutinin-induced lymphocyte transformation in vitro and it has been suggested that this may contribute to its anticataract activity. Following oral administration of bendazac lysine 500mg to healthy subjects mean maximum plasma concentrations of 42 to 49 mg/L were attained within 0.5 to 3 hours. Repeated administration of bendazac lysine 500mg 3 times daily resulted in peak and trough plasma concentrations of approximately 15 to 30 mg/L and 3 to 5 mg/L respectively, within the first 24 hours. Bendazac is more than 99% bound to plasma albumin and has a low volume of distribution (0.16 L/kg). Animal studies have indicated that the drug accumulates in the lens following repeated oral or ocular administration. In healthy subjects, bendazac is eliminated mainly by metabolism to 5-hydroxybendazac, approximately 60% of a dose being excreted in the urine as the major metabolite and its glucuronide. The mean plasma elimination half-life of bendazac was 3.5 hours, while the mean plasma clearance was 0.033 L/h/kg. The pharmacokinetic profile of bendazac was not significantly altered in elderly patients or those with moderate or severe renal impairment; however, an increase in the unbound fraction of bendazac in haemodialysis patients (1% vs 0.4% for healthy subjects) resulted in some minor changes in other pharmacokinetic variables. In patients with severe liver disease, impaired metabolism indicates the need for reduced dosage. There is, at present, no published information regarding the pharmacokinetics of bendazac lysine following ocular administration in humans. Bendazac lysine, usually at a dosage of 500mg 3 times daily orally, has been evaluated in the treatment of cataract in uncontrolled and double-blind placebo-controlled studies of up to 2 years’ duration. Comparison of results between different studies is difficult owing to the variety of methods used for assessment. Data from a very small number of studies using photographic and densitometric methods to objectively study alterations in the transparency of the lens suggest that bendazac lysine treatment can slow the progression of lens opaciflcation. Further studies of this nature in large numbers of patients are required to confirm this finding. Several researchers have reported apparent individual improvements in lens transparency following bendazac lysine treatment, using serial subjective assessment of lens appearance by traditional ophthalmoscopy and biomicroscopy, but this has not been confirmed by objective methods to date. Several studies have documented a significant increase in mean and individual visual acuities in treated groups compared with baseline measurements and analysis of pooled data from controlled trials has indicated that deterioration of visual acuity occurs in a significantly higher proportion of placebo recipients compared with patients receiving bendazac lysine. However, visual acuity testing alone is not regarded as an acceptable method for evaluating the efficacy of an anticataract agent. Controlled clinical trials using visual acuity at variable contrast or contrast sensitivity as parameters have also reported a beneficial effect of bendazac lysine, but in the majority of these studies subjective testing methods have been employed. Treatment with bendazac lysine 500mg 3 times daily orally for 1 year was reported to be effective in reducing the incidence of postoperative cataract development in a group of patients undergoing closed vitrectomy and silicone oil injection for retinal detachment, although further research is required to confirm this preliminary finding. Bendazac lysine eyedrops 0.5%, at a dosage of 2 drops 3 times daily, have been evaluated in a small number of open and placebo-controlled studies, with results comparable to those obtained with the oral formulation. At present, clinical experience with bendazac lysine is limited and it is not possible to give accurate incidence rates for individual adverse effects. However, oral bendazac lysine appears to have been well tolerated in therapeutic trials of up to 2 years’ duration. Gastrointestinal symptoms such as gastralgia, nausea and a dose responsive laxative effect have been the most frequently encountered problems. Bendazac lysine eyedrops 0.5% have been well tolerated; a transient burning sensation on instillation has been the most frequently reported adverse symptom. The recommended starting oral dosage of bendazac lysine is 500mg (adults) or 250mg (children) 3 times daily after meals, with temporary dosage reduction if a laxative effect occurs. Courses of 3 to 6 months are recommended, with regular monitoring of liver function during prolonged treatment. Bendazac dosages should be halved in patients with severe liver disease and concurrent treatment with choleretic drugs should be avoided. For ocular treatment, instillation of 2 drops of a 0.5% solution 3 times daily is recommended.