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Oral contraceptives induce CYP2A6 activity and accelerate nicotine metabolism
Author(s) -
Benowitz N. L.,
Swan G. L.,
Lessov C. N.,
Jacob P.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.135
Subject(s) - cyp2a6 , nicotine , metabolism , cotinine , metabolite , chemistry , hormone , pharmacology , transplacental , medicine , physiology , endocrinology , pregnancy , fetus , placenta , biology , cytochrome p450 , cyp1a2 , genetics
CYP2A6 is the primary enzyme catalyzing the metabolism of nicotine (NIC) and its proximate metabolite cotinine (COT). Pregnancy accelerates NIC and COT metabolism, suggesting that CYP2A6 activity is modulated by sex hormones. We hypothesize that sex hormones administered as oral contraceptives (OC) also induce CYP2A6 activity. Two hundred ninety healthy participants in a twin study of the genetics of NIC metabolism received IV infusions of deuterium‐labeled NIC and COT, with blood sampling to determine disposition kinetics. Women taking OC had substantially faster clearance (CL) of NIC and COT, and CL or NIC via the COT pathway, the latter an indicator of CYP2A6 activity, compared to women not taking OC or compared to men. CL values were also significantly higher in women not taking OC compared to men. (See Table) These findings indicate that OC use accelerates the metabolism of NIC and COT and suggests induction of CYP2A6 activity. This is in contrast to most other reports of OCs inhibiting oxidative metabolism. Insofar as smokers smoke to obtain desired levels of nicotine in the body, OC use might influence cigarette consumption. Clinical Pharmacology & Therapeutics (2004) 75 , P36–P36; doi: 10.1016/j.clpt.2003.11.135Women on OC Women no OC MenN 46 158 86 CL‐nic (ml/min/kg) 23.0 ± 6.3 * 17.7 ± 16.2 † 15.6 ± 4.3 CL‐cot (ml/min/kg) 0.97 ± 0.37 * 0.73 ± 0.4 † 0.58 ± 0.2 CL‐nic⇒cot (ml/min/kg 17.0 ± 6.5 * 13.8 ± 6.1 † 11.8 ± 4.3* Different than women not taking OC and men; † different than men; both p<0.05.