Inhibition of theophylline metabolism by long-term allopurinol administration

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Abstract
Administration to human subjects of an oral dose of allopurinol (300 mg every 12 h) for 14 consecutive days increased the mean theophylline area under the curve (AUC) 27% and mean theophylline half-life (t1/2) 25%, but the mean theophylline clearance (Cl) decreased 21%. Allopurinol did not alter apparent volume of distribution (aVd) or gastrointestinal absorption (Cmax [maximum concentration] and tmax [time to reach Cmax]) of theophylline. After 28 consecutive days of allopurinol administration, theophylline disposition was the same as that on day 14. Given a dose of 300 mg every 12 h for 14 or 28 days, allopurinol inhibits theophylline metabolism, despite the failure of allopurinol in lower doses given for only 7 days to alter theophylline disposition. Several different doses and durations of administration within therapeutic ranges should be studied before firm conclusions can be drawn concerning the influence of 1 drug on the disposition of another.

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