Drug Interactions with Angiotensin Receptor Blockers: Role of Human Cytochromes P450

Abstract

This review summarize the available data on cytochrome P450 - related drug-drug interactions reported in the literature for the eight ARBs. Knowledge of the pharmacokinetic properties of the ARBs should allow the avoidance of the majority of drug interactions without compromising therapeutic benefits.

Acute Kidney Injury from Excessive Potentiation of Calcium-channel Blocker via Synergistic CYP3A4 Inhibition by Clarithromycin Plus Voriconazole

“…In the present case, clarithromycin further lowered the blood pressure after it had already been lowered by voriconazole. In addition, the CYP3A4 system has less influence on the metabolism of other co-prescribed antihypertensive medications: olmesartan, furosemide, and trichlormethiazide (7,8). These findings indicate that the combination of clarithromycin plus voriconazole further raised the nifedipine concentration, inducing hypotension by their synergistic CYP3A4 inhibition.…”

Pharmacogenomics of CYP2C9: Functional and Clinical Considerations

“…Certain other sartan family members namely ibresartan [ 52 ] and, to a more limited extent candesartan [ 53 ] and valsartan [ 54 ], are also CYP2C9 substrates, but active metabolites are not generated. Other sartan family members are not metabolized by P450 [ 55 ]. In addition to prescribed drugs, CYP2C9 contributes to arachidonic acid metabolism with a role in the formation of epoxyeicosatrienoic acids (EETs) [ 56 ].…”

“…However, in North America at least, several large teaching hospitals and research institutions (e.g., Vanderbilt, St. Jude, Mayo Clinic) are actively evaluating the impact of prospective genotyping for an array of pharmacogenes, as is evident from other contributions to this Special Issue. Justification for this comes, in part, from the realization that in any given patient population the proportion that possess an ‘actionable pharmacogene’ is very high, exceeding 90% [ 55 , 199 ]. This term has been coined by the Clinical Pharmacogenetics Implementation consortium (CPIC), which has the goal ‘to help clinicians understand how available genetic test results should be used to optimize drug therapy’ [ 200 ].…”

Interrelation of Antihypertensive Effect of Combination of Valsartan and Amlodipine With Various Polymorphic Variants of Genes Cyp2c9 and Cyp11b2 in Patients With Obesity

“…Имеются данные о влиянии разных полиморфизмов CYP2C9 на фармакокинетику БРА. Установлено, что наличие аллелей *2 и *3 часто приводит к замедлению метаболизма лекарственных средств, увеличивая тем самым их концентрацию и снижая клиренс [3,12,13,14]. В таких ситуациях может значительно меняться их действие и клиническая эффективность.…”

“…Таким образом, можно предполагать большую антигипертензивную эффективность препаратов этой группы у пациентов с высокой активностью альдостеронсинтазы. Вместе с тем взаимосвязь между полиморфизмами генов CYP2C9, CYP11B2 и антигипертензивными эффектами лекарственных средств, в том числе блокаторов РААС, недостаточно изучена [12,13,18].…”