D2-nicotine and its metabolites were measured 30, 150 and 240 min following oral administration. We had predicted that phenotypes would best correlate with CYP2A6 genotype at earlier time-points. To test this we repeated the above analysis with parameter estimates based on the ratio of D2-cotinine: (D2-nicotine + D2-cotinine) after 150 (R2 = 0.710 ) and 240 min (R2 = 0.417 ), as well as the ratio of (D2-trans-3′-hydroxycotinine+ D2-cotinine): (D2-nicotine + D2-cotinine + D2-trans-3′-hydroxycotinine)after 240 min (R2 = 0.554) which accounts for the metabolism of D2-cotinine to D2-trans-3′-hydroxycotinine.
