Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

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262 Applying Pharmacogenomics in Therapeuticstherefore polymorphisms in drug-metabolizing enzymes and drug transporters thatalter the systemic exposure to the substrate drugs or active components of herbs mayaffect the risk of interactions.Case ReportA case report described an interaction of St. John’s wort (Hypericum perforatum)with clozapine via inducing P450s, especially CYP1A2 and CYP3A4. A 41-year-oldwoman with disorganized schizophrenia was stable on a fixed daily dose of 500 mg,with stable plasma level (0.46–0.57 mg/L) of clozapine for the last six months.However, it was revealed that she had started using St. John’s wort (three tabletsdaily, 300 mg per tablet) shortly before the first measurement of a low plasmaclozapine concentration (0.19 mg/L). A month after discontinuation of St. John’swort, the clozapine concentration was 0.32 mg/L, and after one month thereafterit was 0.41 mg/L. Also, the psychiatric condition of the patient was improved. 31 Asthe author discussed, St. John’s wort may pharmacokinetically interact with clozapinethrough inducing CYP3A4, CYP1A2, CYP2C9, and CYP2C19, all of whichare responsible for clozapine metabolism. In addition, P-glycoprotein can also beinduced by this herb. This eventually leads to decreased plasma clozapine levelsand diminished effectiveness. In another case report, Ginkgo biloba can negativelyinfluence the effect of antiretroviral drug efavirenz (EFV) in an HIV-infected malepatient. This may be due to the induction of G. biloba on CYP2B6 and CYP3A4,both of which are the drug-metabolizing enzymes for EFV. 32 We can believe thatboth the genetic polymorphisms and medicines or herbal products can cause thevariations of enzymes’ activities in individuals.St. John’s WortSt. John’s wort is an herb most commonly used for depression and conditions suchas anxiety, tiredness, loss of appetite, and trouble sleeping. There is some strongevidence that it is effective for mild-to-moderate depression. Currently, there havebeen 95 drugs (296 brand and generic names) known to have a major interaction withSt. John’s wort. After administration of St. John’s wort, the AUC 0–∞ of nifedipineand dehydronifedipine decreased by 42.4% and 20.2% in PXR H1/H2 genotype;47.9 and 33.0% in H2/H2 genotypes; whereas for the H1/H1 the AUC 0–∞ of nifedipinedecreased 29.0%, but the AUC 0–∞ of dehydronifedipine increased by 106.7%. 33St. John’s wort treatment significantly increased phenytoin clearance in CYP2C19extensive metabolizers (EMs) but not in poor metabolizers (PMs) and decreasedthe plasma concentrations of omeprazole in a genotype-dependent manner. 34,35Subjects harboring the ABCB1 haplotype comprising 1236C>T, 2677G>T/A, and3435C>T polymorphisms had lower intestinal MDR1 mRNA levels and showed anattenuated inductive response to St. John’s wort as assessed by talinolol disposition. 36The AUC of voriconazole was decreased by 59% with St. John’s wort treatment, witha 144% increase in oral clearance of voriconazole. The apparent oral clearance ofvoriconazole and the absolute increase in apparent oral clearance were smaller inCYP2C19*2 carriers than those with CYP2C19*1/*1 genotype. 37
Pharmacogenomics and Alternative Medicine263GinkgoGinkgo is often used for memory disorders, including Alzheimer disease. It is alsoused for conditions that seem to be due to reduced blood flow in the brain, especiallyin older people. These conditions include memory loss, headache, ringing in the ears,vertigo, difficulty concentrating, mood disturbances, and hearing disorders. Ginkgoenhanced omeprazole hydroxylation in a CYP2C19 genotype-dependent manner.The decrease was greater in CYP2C19 PMs (*2, *3) than EMs. 38BaicalinBaicalin is a flavone glucuronide purified from the medicinal plant Radix scutellariaethrough uridine diphosphate glucuronation. Nowadays, baicalin has begunto be used in bilirubin-lowering therapy, both prescribed and over the counter, inChina. The mean changes in AUC ratio of bupropion was lower for subjects withCYP2B6*6/*6 genotype compared with those with CYP2B6*1/*1 genotype followingbaicalin use, indicating induction of CYP2B6-catalyzed bupropion hydroxylationby baicalin. And administration of baicalin decreased the AUC 0–∞ of rosuvastatinby about 42%, 24%, and 1.8% in carriers of the SLCO1B1 *1b/*1b, *1b/*15, and*15/*15, respectively. 39,40GarlicGarlic is widely used worldwide for its pungent flavor as a seasoning or condiment.There is some scientific evidence that garlic can lower high cholesterol after a fewmonths of treatment. Garlic seems to also lower blood pressure in people with highblood pressure and possibly slow “hardening of the arteries.” There is also someevidence that eating garlic might reduce the chance of developing some cancers suchas cancer of the colon, and possibly of stomach and prostate. Coadministration ofgarlic did not significantly alter warfarin pharmacokinetics or pharmacodynamics.However, subjects with the VKORC1 wild-type genotype showed an increase in theS-warfarin EC50 when warfarin was administered with garlic. 41Grapefruit JuiceGrapefruit juice, a potent inhibitor of CYP3A4, can affect the metabolism of a varietyof drugs, increasing their bioavailability. In some cases, it can lead to a fatalinteraction with drugs such as astemizole or terfenadine. Grapefruit juice significantlyincreased total AUC of lansoprazole in CYP2C19 PMs, and the total AUCof lansoprazole sulfonic/lansoprazole was significantly decreased in CYP2C19EMs (*1/*1). 42 Homozygous wild-type genotype of ABCB1 3435C>T, but not theother genotypes, showed a significant decrease in the active metabolite carebastineurinary excretion after grapefruit juice. 43Cranberry JuiceCranberry juice contains phytochemicals, which may help prevent cancer and cardiovasculardiseases. Cranberry juice is high in oxalate and has been suggested to
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DedicationWe dedicate this book to
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viiiContentsChapter 10 Pharmacogeno
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EditorsXiaodong Feng, PhD, PharmD,
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ContributorsWeiguo Chen, PhDDepartm
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1Concepts inPharmacogenomics andPer
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8Clinical Applicationsof Pharmacoge
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Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

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