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  • Title: Dose-dependent pharmacokinetics of tocainide in the rat.
    Author: Venkataramanan R, Axelson JE.
    Journal: J Pharmacol Exp Ther; 1980 Oct; 215(1):231-4. PubMed ID: 6778990.
    Abstract:
    The pharmacokinetics of tocainide, an experimental antiarrthymic agents, were studied in rats. The concentration of intact drug in plasma and urine samples was determined by an electron capture detector gas chromatographic method. Plasma level and urinary excretion studies revealed the existence of nonlinear kinetics of disposition at and above a 20 mg/kg dose of tocainide. The area under the plasma concentration-time curve increased in a nonlinear fashion with an increase in the dose. Below a 20 mg/kg dose about 19% of the dose was excreted as intact drug in urine while at and above this dose level at least a 100% increase in excretion of intact drug was observed. The extent of inhibition of tocainide metabolism by SKF 525A is more pronounced at a 15 mg/kg dose of tocainide than at 20 mg/kg which suggests that the observed nonlinearity at 20 mg/kg is due to saturation of the metabolism of tocaininde. Study of the effect of route of administration reveals that tocainide is completely absorbed up to a dose of 15 mg/kg, following p.o. or i.p. administration.
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