雷诺嗪的临床药代动力学。
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Jerling米
雷诺嗪的临床药代动力学。
临床药典杂志。2006;45(5):469-91。doi: 10.2165 / 00003088-200645050-00003。
- PubMed ID
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16640453 (PubMed视图］
- 摘要
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Ranolazine是美国FDA批准的一种化合物，用于与氨氯地平、β -肾上腺素受体拮抗剂或硝酸盐联合治疗慢性心绞痛，用于其他抗心绞痛药物未达到充分反应的患者。雷诺嗪的抗心绞痛作用不依赖于心率或血压的变化。它通过不同的药理学机制起作用，其中抑制晚期向内钠电流(减少钙过载，从而减少左室舒张张力)是减少耗氧量的一种合理机制。最初的研究使用口服溶液或立即释放(IR)胶囊，但随后开发了一种缓释(ER)配方，以允许每天两次给药并保持疗效。口服溶液或IR胶囊后，1小时内观察到峰值血药浓度(C(max))。给药后放射标记的雷诺嗪，73%的剂量随尿液排出，不变的雷诺嗪在尿液和粪便中的放射性均小于5%。绝对生物利用度为35% ~ 50%。食物对ER配方的吸收速率或程度没有影响。Ranolazine蛋白结合在治疗浓度范围内约为61-64%。在稳定状态下，Ranolazine的分布体积在85 ~ 180 l之间。Ranolazine被细胞色素P450 (CYP) 3A酶广泛代谢，并在较小程度上被CYP2D6代谢，约5%的Ranolazine在肾脏中排泄不变。 Elimination half-life of ranolazine is 1.4-1.9 hours but is apparently prolonged, on average, to 7 hours for the ER formulation as a result of extended absorption (flip-flop kinetics). Elimination occurs through parallel linear and saturable elimination pathways, where the saturable pathway is related to CYP2D6, which is partly inhibited by ranolazine. Oral plasma clearance diminishes with dose from, on average, 45 L/h at 500 mg twice daily to 33 L/h at 1000 mg twice daily. The departure from dose proportionality for this dose range is modest, with increases in steady-state C(max) and area under plasma concentration-time curve (AUC) from 0 to 12 hours of 2.5- and 2.7-fold, respectively. Ranolazine pharmacokinetics are unaffected by sex, congestive heart failure and diabetes mellitus. AUC increases up to 2-fold with advancing degree of renal impairment. Ranolazine is a weak inhibitor of CYP3A, and increases AUC and C(max) for simvastatin, its metabolites and HMG-CoA reductase inhibitor activity <2-fold. Digoxin AUC is increased 40-60% by ranolazine through P-glycoprotein inhibition. Ranolazine AUC is increased by CYP3A inhibitors ranging from 1.5-fold for diltiazem 180 mg once daily to 3.9-fold for ketoconazole 200 mg twice daily. Verapamil increases ranolazine exposure approximately 2-fold. CYP2D6 inhibition has a negligible effect on ranolazine exposure.
引用本文的药物库数据
- 药物
- 药物靶点
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药物 目标 种类 生物 药理作用 行动 Ranolazine 钠通道蛋白(蛋白质组) 蛋白质组 人类 未知的抑制剂细节 - 药物的相互作用Learn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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药物 交互 整合药物之间
软件中的交互醋丁洛尔 Ranolazine 乙酰丁醇与雷诺嗪合用可提高血清浓度。 Almotriptan Ranolazine 阿莫曲坦与雷诺嗪合用可提高血清浓度。 Alogliptin Ranolazine 阿格列汀与雷诺嗪合用可提高血清浓度。 氨基比林 Ranolazine 氨苯氮酮与雷诺嗪合用可提高血清浓度。 阿莫沙平 Ranolazine 阿莫沙平与雷诺嗪合用可提高血清浓度。 安非他命 Ranolazine 安非他明与雷诺嗪合用可提高血清浓度。 安替比林 Ranolazine 安替比林与雷诺嗪合用可提高血清浓度。 Arformoterol Ranolazine 阿福莫特罗与雷诺嗪合用可提高血清浓度。 阿立哌唑 Ranolazine 阿立哌唑与雷诺嗪合用可提高血清浓度。 阿立哌唑lauroxil Ranolazine 阿立哌唑与雷诺嗪合用可提高血清浓度。
