Inhibition of theophylline metabolism by long-term allopurinol administration

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.