盐酸cinacalcet临床药代动力学和药效学的状况。

文章的细节

引用
复制到剪贴板

Padhi D,哈里斯R

盐酸cinacalcet临床药代动力学和药效学的状况。

48 Pharmacokinet。2009; (5): 303 - 11。doi: 10.2165 / 00003088-200948050-00002。

PubMed ID
19566113 (在PubMed
]
文摘

Cinacalcet盐酸盐(Cinacalcet)是一个calcimimetic批准治疗继发性甲状旁腺功能亢进的患者的慢性肾脏疾病(CKD)接受透析治疗患者的血钙过多的甲状旁腺癌。口服后,血浆浓度峰值cinacalcet在2 - 6小时内发生。绝对生物利用度是20 - 25%,管理cinacalcet较低或高脂肪膳食增加曝光(血浆浓度时间曲线下面积的0到无穷大(AUC(∞))) 1.5 - 1.8倍。Cinacalcet盐酸与碳酸钙或sevelamer没有显著的交互作用,磷酸盐粘结剂中常用的治疗CKD患者接受透析。终端消除半衰期是30 - 40小时,稳态浓度达到7天内。cinacalcet的药物代谢动力学情况是剂量比例超过30 - 180毫克的剂量范围。cinacalcet的药动学特征不明显受到不同程度的肾功能损害的影响。的药物动力学cinacalcet健康受试者之间具有可比性,原发性甲状旁腺功能亢进患者和继发性甲状旁腺功能亢进患者肾功能下降(包括继发性甲状旁腺功能亢进患者接受透析)。此外,cinacalcet的药物代谢动力学情况是类似的继发性甲状旁腺功能亢进患者接受血液透析和继发性甲状旁腺功能亢进患者接受腹膜透析。轻度肝障碍并不影响cinacalcet的药物动力学,而中度或重度肝损伤增加曝光(AUC(∞))大约2 - 4倍,分别。 Age, sex, bodyweight and race do not notably affect the pharmacokinetics of cinacalcet. Cinacalcet is extensively metabolized by multiple hepatic cytochrome P450 (CYP) enzymes (primarily 3A4, 2D6 and 1A2) with <1% of the parent drug excreted in the urine. Dose adjustments of cinacalcet may be necessary, and parathyroid hormone (PTH) and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g. ketoconazole, erythromycin, itraconazole). Cinacalcet is a strong inhibitor of CYP2D6; therefore, dose adjustment of concomitant medications that are predominantly metabolized by CYP2D6 and have a narrow therapeutic index (e.g. flecainide, vinblastine, thioridazine and most tricyclic antidepressants) may be required. Cinacalcet does not appreciably inhibit or induce the activities of CYP3A4, 1A2, 2C9 or 2C19. An inverse relationship exists between plasma PTH and cinacalcet concentrations. PTH concentrations are greatest before dose administration when the cinacalcet concentration is lowest (24 hours after the previous day's dose). Nadir PTH levels occur approximately 2-3 hours after dosing.

DrugBank数据引用了这篇文章

药物
药物酶
药物 酶 类 生物 药理作用 行动
Cinacalcet 细胞色素P450 1 a2 蛋白质 人类
未知的
底物
 细节
Cinacalcet 细胞色素P450 2 d6 蛋白质 人类
未知的
抑制剂
 细节
Cinacalcet 细胞色素P450 3 a4 蛋白质 人类
未知的
底物
 细节