EFFECT OF TAMOXIFEN ON THE PHARMACOKINETICS OF THEOPHYLLINE IN RATS

The effect of tamoxifen on the pharmacokinetics of theophylline was in vestigated in male Sprague-Dawley rats. The oral administration of tam oxifen at a dose equal to 40 mg kg(-1), 48 h before the intravenous in jection of theophylline 10 mg kg(-1), significantly (P < 0.05) increas ed the clearance of theophylline by 39%, with no apparent effect on th e volume of distribution. As a consequence, the elimination half-life of theophylline was significantly (P < 0.05) shortened in the tamoxife n-treated rats (3.56 +/- 0.39 h vs 5.25 +/- 0.48 h) as well as its mea n residence time (5.04 +/- 0.60 h vs 7.50 +/- 0.75 h). Although these data cannot be directly extrapolated to the clinical situation, they p rovide experimental support to suggest that more attention should be p aid to the potential risk of pharmacokinetic interactions in the prese nce of tamoxifen.