Effect of tamoxifen on the pharmacokinetics of theophylline in rats.
The effect of tamoxifen on the pharmacokinetics of theophylline was investigated in male Sprague-Dawley rats. The oral administration of tamoxifen at a dose equal to 40 mg kg-1 48 h before the intravenous injection of theophylline 10 mg kg-1, significantly (P < 0.05) increased the clearance of theophylline by 39%, with no apparent effect on the volume of distribution. As a consequence, the elimination half-life of theophylline was significantly (P < 0.05) shortened in the tamoxifen-treated rats (3.56 +/- 0.39 h vs 5.25 +/- 0.48 h) as well as its mean 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 provide experimental support to suggest that more attention should be paid to the potential risk of pharmacokinetic interactions in the presence of tamoxifen.
Poisson
D
D
Laboratoire de Neuropharmacologie, Faculté de Pharmacie, Tours, France.
Dupuis
A
A
Breteau
M
M
Bouquet
S
S
Poterre
M
M
Couet
W
W
D000818:Animals; D001993:Bronchodilator Agents / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*; D013806:Theophylline / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D004965:Estrogen Antagonists; D013629:Tamoxifen; D013806:Theophylline