Table 5.

Examples of established and possible risk modifiers of herb-drug and grapefruit–drug interactions

Risk modifier	Botanical CYP inducer/inhibitor	Conventional drug substrate	CYP system involved	Observed or suggested effect
Age	St John's wort (SJW)	Midazolam	CYP 3A4	Elderly subjects are susceptible to SJW-mediated changes in CYP activity. Comparison with earlier studies that employed young subjects suggests that age-related changes in CYP responsivity to botanical supplementation may exist [53]
Liver cirrhosis (LC)	Grapefruit juice (GJ)	Midazolam	CYP 3A4	Interaction between GJ and oral midazolam was more marked in patients with LC than in earlier study in healthy subjects [54]
Pharmacogenetic status	Ginkgo	Omeprazole	CYP 2C19	Ginkgo significantly induced CYP2C19-mediated hydroxylation of omeprazole and this effect was more pronounced in poor metabolizers than in extensive metabolizers [55]