Pharmacokinetic drug-drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management.
Pharmacokinetic drug-drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management.
复制标题
1,4-二氢吡啶钙通道阻滞剂和他汀类药物之间的药代动力学药物相互作用：决定相互作用强度和相关临床风险管理的因素
DOI：
10.2147/tcrm.s55512
复制
发表时间：
2014
影响因子：
2.8
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Zhou YT;Yu LS;Zeng S;Huang YW;Xu HM;Zhou Q
1，4-二氢吡啶类钙通道阻滞剂（DHP-CCB）与他汀类药物（或3-羟基-3-甲基戊二酰辅酶A [HMG-CoA]还原酶抑制剂）联合给药在高胆固醇血症和高血压患者中很常见。为了降低肌病的风险，2011年，美国食品药品监督管理局（FDA）药物安全性通讯为辛伐他汀设定了一个新的剂量限制，适用于辛伐他汀伴随治疗的患者。然而，对于接受阿托伐他汀治疗的患者，没有这样的剂量限制。阿托伐他汀/阿托伐他汀的组合丸剂制剂可在市场上获得。目前尚未对DHP-CCB与他汀类药物的药代动力学药物相互作用（DDI）特征、不同程度DDI的潜在机制或相应的临床风险管理进行系统评价。通过执行PubMed检索识别相关文献，涵盖时间范围为1987年1月至2013年9月。纳入了药物代谢和药代动力学领域的研究，这些研究描述了DHP-CCB和他汀类药物之间的DDI，或直接比较了与细胞色素P450（CYP）3A 4代谢的他汀类药物或DHP-CCB相关的DDI程度。对每篇文章的全文进行了严格审查，并进行了数据解释。DHP-CCB与他汀类药物联用时发生药代动力学DDI的情况主要有三种：1）他汀类药物作为促凝剂（普伐他汀-尼莫地平和洛伐他汀-尼卡地平）; 2）他汀类药物被指定为目标药物（伊拉地平-洛伐他汀、拉西地平-辛伐他汀、氨氯地平-辛伐他汀、贝尼地平-辛伐他汀、阿折地平-辛伐他汀、乐卡地平-辛伐他汀和氨氯地平-阿托伐他汀）;和3）相互作用（乐卡地平-氟伐他汀）。辛伐他汀在肠壁中具有广泛的首过效应，而阿托伐他汀具有较小的肠道首过效应。与辛伐他汀的相互作用似乎主要由肠道水平的CYP 3A 4抑制作用驱动，而与阿托伐他汀的相互作用更多是由于肝脏CYP 3A 4抑制作用。与阿托伐他汀相比，CYP 3A 4抑制剂与辛伐他汀的相互作用更明显。从目前的数据来看，阿托伐他汀似乎是与DHP-CCB联合用药的更安全的CYP 3A 4-他汀类药物。从CYP 3A 4介导的药物代谢的角度来看，没有令人信服的证据表明，无论是作为沉淀剂药物还是作为目标药物，DHP-CCB都是一种不寻常的DHP-CCB。除了与CYP 3A 4相互作用外，Amaldine还可能与CYP 3A 5相互作用，这可以解释其与其他DHP-CCB相比的特殊特征。DHP-CCB与他汀类药物之间的药物依赖性程度及临床结局取决于多种因素，如他汀类药物的种类、DHP-CCB的理化性质、沉淀药物或目标药物的剂量、患者的性别等（例如，伊拉地平-洛伐他汀），给药途径（例如，口服与静脉内尼卡地平-洛伐他汀），给药方案（例如，非同时给药方法与同时给药方法）和药物遗传学状态（例如，CYP 3A 5非表达者与CYP 3A 5表达者）。临床专业人员应加强两类药物联合使用的风险管理，提高对疗效和药物不良反应的潜在变化的认识，合理处方替代药物，注意剂量调整和给药方案，审查医嘱的适当性。需要进一步研究-从药代动力学或临床角度来看，DHP-CCB和他汀类药物之间的DDI尚未在人体中进行研究;此外，DHP-CCB与他汀类药物的不同药代动力学相互作用的强度应通过系统研究来解决。
Coadministration of 1,4-dihydropyridine calcium channel blockers (DHP-CCBs) with statins (or 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) is common for patients with hypercholesterolemia and hypertension. To reduce the risk of myopathy, in 2011, the US Food and Drug Administration (FDA) Drug Safety Communication set a new dose limitation for simvastatin, for patients taking simvastatin concomitantly with amlodipine. However, there is no such dose limitation for atorvastatin for patients receiving amlodipine. The combination pill formulation of amlodipine/atorvastatin is available on the market. There been no systematic review of the pharmacokinetic drug–drug interaction (DDI) profile of DHP-CCBs with statins, the underlying mechanisms for DDIs of different degree, or the corresponding management of clinical risk. The relevant literature was identified by performing a PubMed search, covering the period from January 1987 to September 2013. Studies in the field of drug metabolism and pharmacokinetics that described DDIs between DHP-CCB and statin or that directly compared the degree of DDIs associated with cytochrome P450 (CYP)3A4-metabolized statins or DHP-CCBs were included. The full text of each article was critically reviewed, and data interpretation was performed. There were three circumstances related to pharmacokinetic DDIs in the combined use of DHP-CCB and statin: 1) statin is comedicated as the precipitant drug (pravastatin–nimodipine and lovastatin–nicardipine); 2) statin is comedicated as the object drug (isradipine–lovastatin, lacidipine–simvastatin, amlodipine–simvastatin, benidipine-simvastatin, azelnidipine– simvastatin, lercanidipine–simvastatin, and amlodipine–atorvastatin); and 3) mutual interactions (lercanidipine–fluvastatin). Simvastatin has an extensive first-pass effect in the intestinal wall, whereas atorvastatin has a smaller intestinal first-pass effect. The interaction with simvastatin seems mainly driven by CYP3A4 inhibition at the intestinal level, whereas the interaction with atorvastatin is more due to hepatic CYP3A4 inhibition. The interaction of CYP3A4 inhibitor with simvastatin has been more pronounced compared with atorvastatin. From the current data, atorvastatin seems to be a safer CYP3A4-statin for comedication with DHP-CCB. There is no convincing evidence that amlodipine is an unusual DHP-CCB, either as a precipitant drug or as an object drug, from the perspective of CYP3A4-mediated drug metabolism. Amlodipine may have interactions with CYP3A5 in addition to CYP3A4, which may explain its particular characteristics in comparison with other DHP-CCBs. The degree of DDIs between the DHP-CCB and statin and the clinical outcome depends on many factors, such as the kind of statin, physicochemical proprieties of the DHP-CCB, the dose of either the precipitant drug or the object drug, the sex of the patient (eg, isradipine–lovastatin), route of drug administration (eg, oral versus intravenous nicardipine–lovastatin), the administration schedule (eg, nonconcurrent dosing method versus concurrent dosing method), and the pharmacogenetic status (eg, CYP3A5-nonexpressers versus CYP3A5-expressers). Clinical professionals should enhance risk management regarding the combination use of two classes of drugs by increasing their awareness of the potential changes in therapeutic efficacy and adverse drug reactions, by rationally prescribing alternatives, by paying attention to dose adjustment and the administration schedule, and by review of the appropriateness of physician orders. Further study is needed – the DDIs between DHP-CCBs and statins have not all been studied in humans, from either a pharmacokinetic or a clinical perspective; also, the strength of the different pharmacokinetic interactions of DHP-CCBs with statins should be addressed by systematic investigations.
影响因子：
--
作者：
Wiwanitkit S;Wiwanitkit V
通讯作者：
Wiwanitkit V