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  • Title: Effect of mexiletine on elimination and metabolic conversion of theophylline and its major metabolites in rats.
    Author: Ogiso T, Iwaki M, Tanino T, Okuyama K, Uno S.
    Journal: Biol Pharm Bull; 1993 Feb; 16(2):163-7. PubMed ID: 8364452.
    Abstract:
    In an attempt to clarify the possible mechanism of the interaction between theophylline (TP) and mexiletine (ME), the elimination kinetics and in vitro metabolism of TP and its metabolites were investigated in rats. The plasma elimination of TP, 1,3-dimethyluric acid (1,3-DMU) and 1-methyluric acid (1-MU) was significantly delayed by the intravenous (i.v.) administration of ME. The oral administration of ME also decreased the elimination rate of TP to the same extent as the i.v. dosing. The in vitro metabolic experiment showed that ME significantly inhibited the metabolic conversion of TP to 1,3-DMU and, 1,3-DMU to 1-MU, and slightly inhibited the conversion of TP to 3-methylxanthine, these processes being mediated by microsomal enzymes, with no inhibition of xanthine oxidase. Our results indicated that ME could inhibit the metabolic conversion of TP and its metabolite in rat, as reported in man.
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