Cinnamon ( Cinnamomum spp.) is used as a culinary spice and dietary supplement. A major constituent, cinnamaldehyde, was previously shown to inactivate cytochrome P450 (CYP) 2A6 in vitro. A mechanistic static model predicted an ~5‐fold increase in the AUC of the CYP2A6 substrates nicotine and letrozole. Accordingly, the effects of a well‐characterized cinnamon ( Cinnamomum verum ) product on the pharmacokinetics of nicotine and letrozole were evaluated in 16 healthy, non‐nicotine using adults. They were administered a single dose of nicotine gum (2 mg) or letrozole tablet (2.5 mg) (baseline). After a sufficient washout (2–14 days), they self‐administered C. verum (2 g thrice daily) for 5 consecutive days. On Day 6, they were administered C. verum with nicotine or letrozole, followed by two more doses of C. verum (cinnamon exposure). Plasma was collected from 0 to 12 (nicotine) or 0–240 (letrozole) hours. The geometric mean plasma concentration vs. time profile for both drugs was nearly superimposable in the presence vs. absence of C. verum . The geometric mean ratio (GMR) 90% confidence interval of the AUC of nicotine and letrozole in the presence to absence of cinnamon was 0.98 0.96–1.12 and 1.11 0.98–1.24, respectively ( P > 0.16), indicating no interactions. Application of the “slope approach” involving the 3‐hydroxycotinine‐to‐cotinine ratio provided potential new mechanistic insight into CYP2A6 inhibition. The general lack of effect of a typical dosage of C. verum on the pharmacokinetics of nicotine and letrozole suggests that C. verum may be safe to consume with both drugs, as well as other CYP2A6 substrates.
Nguyen et al. (Sun,) studied this question.