J. Agric. Food Chem. 2022, 70, 8, 2752–2761

Publication Date:February 1, 2022

https://doi.org/10.1021/acs.jafc.2c00237

Among the top 10 foods that contain a large variety of inhibitors, black pepper (Piper nigrum) leads with 20 different candidate compounds, of which only five were previously acknowledged as inhibitors. Other food families are herbal teas, citrus fruit, the unique Ginkgo biloba, jicama (Pachyrhizus erosus), and sweet bay (Laurus nobilis), each with more than 10 different compounds predicted to be CYP3A4 inhibitors (Figure 3B). Myristicin (prediction index = 0.76; experimental IC50 < 43 (24)) appears in sufficient concentrations in parsnip (Pastinaca sativa), parsley (Petroselinum crispum), mace (Myristica fragrans), caraway (Carum carvi), and carrot (Daucus carota) (content levels: 42 g/100 g, 1.7 g/100 g, 0.68 g/100 g, 24 mg/100 g, and 1.7 mg/100 g, respectively). A serving of red wine (150 mL) contains 1 mg of viniferin (prediction index = 0.73).

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the level of enzyme can significantly affect the required dose

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The normalized concentrations of clonazepam were significantly higher in the patients displaying low CYP3A4 mRNA levels (1263.5±482.9ng/mL per mg/kg bodyweight) than normal CYP3A4 expressers (558.5±202.4ng/mL per mg/kg bodyweight) (P<.0001) (Figure 2b). The normalized clonazepam concentration in the patient expressing CYP3A4 at high level (452.6ng/mL per mg/kg bodyweight) was comparable with those in the normal expresser patients. The models proposed significantly higher daily dose of clonazepam for the patients expressing CYP3A4 at normal level than for those with low CYP3A4 mRNA level (the dose range of 4.47–7.84mg vs 2.23–4.22mg, P<.0001), whereas the dosage applied in the clinical practice was considered to be the same for low and normal CYP3A4 expresser patients (2.28±1.56mg vs 2.47±1.58mg, P=.5237).