Bicalutamide:临床药物动力学和代谢。

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Cockshott ID

Bicalutamide:临床药物动力学和代谢。

Pharmacokinet。2004年,43 (13):855 - 78。

PubMed ID

15509184 (在PubMed

]

文摘

Bicalutamide是一种非甾体类纯抗雄激素每天摄入150毫克的剂量一次作为单一疗法治疗早期(局部或局部晚期)nonmetastatic前列腺癌。使用50毫克的剂量每天一次结合luteinising激素释放激素类似物或手术阉割治疗晚期前列腺癌。Bicalutamide是外消旋体及其antiandrogenic活动位于(R)对映体,几乎只在很少,如果有的话,活动(S)对映体。(R) -Bicalutamide是缓慢和饱和吸收,但吸收不受食物的影响。它有一个长等离子体消除半衰期(1周)在等离子体在日常管理和积累10倍。(S) -Bicalutamide更迅速从等离子体吸收和清除;(R)的稳态浓度(Css) -bicalutamide高出100倍比-bicalutamide(年代)。Css剂量线性增长到50毫克,但非线性高剂量,达到高原高于300毫克。Css比白种人高在日本,但是没有与肾功能损害程度的关系,体重和年龄的存在。虽然轻度到中度肝损害不影响药物动力学,有证据表明(R) -bicalutamide慢消除的对象有严重肝损伤。 Bicalutamide metabolites are excreted almost equally in urine and faeces with little or no unchanged drug excreted in urine; conversely, unchanged drug predominates in plasma. Bicalutamide in faeces is thought to arise from hydrolysis of bicalutamide glucuronide and from unabsorbed drug. Bicalutamide appears to be cleared almost exclusively by metabolism; this is largely mediated by cytochrome P450 (CYP) for (R)-bicalutamide, but glucuronidation is the predominant metabolic route for (S)-bicalutamide. (S)-Bicalutamide is metabolised in vitro by CYP3A4, and it is probable that this isoenzyme is also responsible for the metabolism of (R)-bicalutamide. In vitro data suggest that (R)-bicalutamide has the potential to inhibit CYP3A4 and, to a lesser extent, CYP2C9, 2C19 and 2D6. However, using midazolam as a specific CYP3A4 marker, no clinically relevant inhibition is observed in vivo with bicalutamide 150mg. Although bicalutamide is a CYP inducer in laboratory animals, dosages < or = 150 mg/day have shown no evidence of enzyme induction in humans. Daily administration of bicalutamide increases circulating levels of gonadotrophins and sex hormones; although testosterone increases by up to 80%, concentrations in most patients remain within the normal range. Bicalutamide produces a dose-related decrease in prostate-specific antigen (PSA) at dosages < or = 150 mg/day. However, little relationship is observed between median PSA reduction and (R)-bicalutamide Css.

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药物酶

药物	酶	类	生物	药理作用	行动
Bicalutamide	细胞色素P450 2 c19	蛋白质	人类	未知的	抑制剂	细节
Bicalutamide	细胞色素P450 2 c9	蛋白质	人类	未知的	抑制剂	细节
Bicalutamide	细胞色素P450 2 d6	蛋白质	人类	未知的	抑制剂	细节
Bicalutamide	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂	细节