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  • Title: Studies on theophylline metabolism: autoinduction and inhibition by antipyrine.
    Author: Denlinger CL, Stryker KK, Slusher LB, Vesell ES.
    Journal: Clin Pharmacol Ther; 1987 May; 41(5):522-30. PubMed ID: 3568537.
    Abstract:
    Theophylline metabolism was accelerated in 11 of 13 normal male volunteers who received theophylline for 1 week in usual therapeutic doses (3 mg/kg orally t.i.d.). Mean theophylline clearance increased 24% and mean salivary elimination half-life (t1/2) decreased 16%, whereas the mean apparent volume of distribution of theophylline was unchanged at 0.7 L/kg. Large variations occurred in the extent of autoinduction, ranging from no change in two subjects to doubling of theophylline clearance in two others. Subjects who accelerated their theophylline metabolism exhibited a high inverse correlation between the extent of their induction and their two control values for theophylline clearance (r = -0.88 and -0.91; P less than 0.05). A single oral dose of antipyrine (18 mg/kg) simultaneously coadministered with a single oral dose of theophylline (5 mg/kg) retarded the metabolism of both theophylline and antipyrine. No significant change occurred in the apparent volume of distribution of either drug. Coadministration with antipyrine reduced mean theophylline clearance 18% and increased salivary t1/2 39%. Theophylline decreased mean antipyrine clearance 21% and increased its mean salivary t1/2 28%. Theophylline metabolism, therefore, is sensitive to not only autoinduction when theophylline is given long term at usual therapeutic doses but also inhibition when theophylline is coadministered with certain drugs.
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