Effect of cigarette smoking on coumarin metabolism in humans.
Extant data, mostly from studies in vitro, suggest that coumarin and nicotine are both metabolized by CYP2A6, a cytochrome P450 isozyme. In order to investigate this issue further, the activity of this enzyme in vivo was measured in 37 non-smokers and 37 smokers using coumarin (2.0 mg, PO) as the metabolic probe. The percentage of coumarin metabolized to 7-hydroxycoumarin in 8 h was measured in urine by high-pressure liquid chromatography. There was more than 10-fold variability in coumarin metabolism in both groups. Coumarin metabolism was significantly reduced in smokers (46.6 +/- 4.4%) as compared to non-smokers (66.4 +/- 3.5%; p < or = .001). The results support previous in vitro findings that both coumarin and nicotine are metabolized, at least in part, by a common pathway, which most likely is CYP2A6.
Poland
R E
RE
Cedars-Sinai Medical Center, Department of Psychiatry, 8730 Alden Drive, Room E-135, Los Angeles, CA 90048, USA. polandr@cshs.org
Pechnick
R N
RN
Cloak
C C
CC
Wan
Y J
YJ
Nuccio
I
I
Lin
K M
KM
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases; D003374:Coumarins / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005731:Ganglionic Stimulants / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*
D000925:Anticoagulants; D003374:Coumarins; D005731:Ganglionic Stimulants; D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6