ABSTRACT
The photodegradation process of the phototoxic diuretic drug chlorthalidone was studied. The products of its photolysis under UV-B were isolated and identified. Chlorthalidone was found to be active when examined by photohemolysis on human erythrocytes, but not in the presence of the isolated photoproducts. Inhibition of the photohemolysis process induced by chlorthalidone on addition of reduced glutathione (GSH) or ascorbic acid suggests the involvement of radicals species. The inhibition with 1,4-diazabycyclo [2.2.2] octane (DABCO), sodium azide (NaN3) sowie 2,5-dimethylfuran proof the participation of singlet oxygen (1O2) in this process.
Subject(s)
Chlorthalidone/chemistry , Chlorthalidone/toxicity , Dermatitis, Phototoxic/pathology , Diuretics/chemistry , Diuretics/toxicity , Chlorthalidone/radiation effects , Chromatography, High Pressure Liquid , Diuretics/radiation effects , Electron Transport , Erythrocytes/drug effects , Free Radicals , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Photochemistry , Photolysis , Ultraviolet RaysABSTRACT
Celiprolol hydrochloride is a highly cardioselective beta1-adrenergic antagonist with a unique pharmacologic profile. The adverse experience safety data derived from 18 double-blind trials (n = 2884) were evaluated. The results demonstrated a wide margin of safety for celiprolol over the recommended dosage range of 200 to 600 mg once daily. Celiprolol exhibited an adverse experience profile similar to that of placebo and resulted in a lower incidence of bradycardia and age-associated increases in adverse event rates compared with atenolol and propranolol.
