Drug Metabolism and Variability

To the Editor: In his review, Wilkinson (May 26 issue) 1 mentions grapefruit juice among inducers or inhibitors of various cytochrome P-450 enzymes. Another nonpharmaceutical interaction may be equally important, because of its constant occurrence in users — tobacco. Smoking induces CYP1A2 activity, 2 possibly causing a reduced effect of its substrates (e.g., estradiol). Among postmenopausal women receiving 1 or 2 mg daily of oral estrogen, we found that the serum estradiol level in smokers was half that in nonsmokers. 3 , 4 The effect was manifested by about a 50 percent reduction in breast tenderness in smokers. 5 Whereas smokers being treated with 1 . . .