The effect of cigarette smoking on drug metabolism in the liver and placenta: the use of cotinine in verifying smoking status.
Placental and hepatic xenobiotic-metabolising activities were studied in smokers and non-smokers, who were classified by anamnestic interview, plasma thiocyanate and plasma cotinine determinations. Plasma thiocyanate assay is inadequate in the classification of smokers and non-smokers. Plasma cotinine levels reflect more accurately the smoking status. The anamnestic smokers remained smokers and several self-declared non-smokers proved to be smokers. On the basis of plasma cotinine determination all real smokers had higher 7-ethoxyresorufin 0-deethylase (ERDE) activities measured either in placental microsomes or liver biopsy homogenates than non-smokers. Classification based on plasma cotinine levels showed a statistically significant (P less than 0.001) difference between smokers and non-smokers in liver homogenate ERDE activity. However, cotinine levels did not correlate with any of the xenobiotic-metabolising activities tested. An objective biochemical marker, such as cotinine determination seems to be necessary when evaluating the effect of smoking on drug metabolism in man.
Pasanen
M
M
Department of Pharmacology, University of Oulu, Finland.
Vahakangas
K
K
Sotaniemi
E A
EA
Pelkonen
O
O
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D003367:Cotinine / Q000097:blood*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011760:Pyrrolidinones / Q000097:blood*; D012907:Smoking / Q000097:blood / Q000378:metabolism*; D013861:Thiocyanates / Q000097:blood
D004364:Pharmaceutical Preparations; D011760:Pyrrolidinones; D013861:Thiocyanates; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D003367:Cotinine