Pharmacogenomics and Herb-Drug Interactions: Merge of Future and Tradition
Table 1
Metabolic enzyme gene polymorphisms and HDIs.
Herbal medicines
Drugs
Genes
Polymorphisms
Pharmacogenomics in HDIs effects
References
Baicalin
Bupropion
CYP2B6
1/1, 1/6, 6/6
The AUC ratio of hydroxybupropion to bupropion tended to be more pronounced lower in 6/6 compared with 1/1 genotype patients (5.3 versus 8.0) after baicalin treatment.
Echinacea dosing reduced the oral clearance of dextromethorphan by 28% and increased AUC by 42% in the CYP2D6 poor metabolizers, while extensive metabolizers were not affected.
After G. biloba, the mean decreases in omeprazole were 41.5%, 27.2%, and 40.4% in the homozygous Ems and heterozygous EMs and PMs, whereas the decreases in omeprazole sulfoneomeprazole sulfone were 41.2%, 36.0%, and 36.0%, respectively.
GFJ treatment significantly increased total AUC of lansoprazole (26661 ± 7407 versus 34487 ± 10850 ng⋅h/mL) in 2/2 and 2/3 subjects, whereas it was significantly decreased (0.07 ± 0.05 versus 0.04 ± 0.05) in 1/1 genotype carries.
homEMs (1/1) hetEMs (1/2 and 1/3); PMs (2/2 and 2/3)
The mean plasma concentrations of lansoprazole were not increased by GFJ, whereas GFJ slightly prolonged the in the three different CYP2C19 genotype groups.
Omeprazole, dextromethorphan hydrobromide, and midazolam
CYP2C19, CYP2D6, CYP3A4
CYP2C191/1 CYP2C192/2
LDW is unlikely to cause pharmacokinetic interaction when it is combined with other medications predominantly metabolized by CYP2C19, CYP2D6, and CYP3A4 enzymes.
The metabolic ratio of losartan (ratio of of E-3174 to of losartan) after a 14-day treatment with silymarin decreased significantly higher in individuals with the CYP2C91/1 genotype (48.78 ± 25.85%) than the CYP2C91/3 genotype (20.09 ± 16.87%).
Administration of St. John’s wort induces higher metabolic activity of CYP3A4 in H1/H1 than in H1/H2 and H2/H2 subjects, with the of Nifedipine decreased by 42.4% (H1/H2), 47.9% (H2/H2), and 29.0% (H1/H1), whereas that of dehydronifedipine increased by 20.2%, 33.0%, and 106.7%.
Treatment with St. John’s wort significantly increases the apparent clearance of gliclazide by 50%. For CYP2C92 allele carriers, the increase is slightly lower.
The AUC of voriconazole was increased by 22% the first day and decreased by 59% after 15 days, with a 144% increase (carriers of 1 or 2 deficient CYP2C192 alleles were smaller than wild-type carries) in its oral clearance (CL/F) after St. John's wort administration.
St. John’s wort can induce CYP3A4 and increase higher CYP2C19 activity in wild-type than poor metabolizers (2/2 or 2/3), leading to increased metabolites of omeprazole in genotype-dependent manner.
St. John’s wort treatment significantly increased CYP2C19 activity in 1/1 subjects, with mephenytoin metabolites excretion raised by 151.5% ± 91.9%, which is in contrast to 2/2 and 2/3 individuals.
The effective ratio of subjects with homozygotes (AA) of the wild-type allele of TPMTrs1142345 was 2.8 times higher than that of subjects with TPMT heterozygotes (AG).
YZH induces CYP3A4 and CYP2C19 metabolism of omeprazole with the decrease of the ratio of omeprazole/5-hydroxyomprazole in CYP2C191/1 and CYP2C191/2 or 3 greater than in CYP2C192/2.
