临床solifenacin的药代学和药效学。
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Doroshyenko O,富U
临床solifenacin的药代学和药效学。
48 Pharmacokinet。2009; (5): 281 - 302。doi: 10.2165 / 00003088-200948050-00001。
- PubMed ID
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19566112 (在PubMed]
- 文摘
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solifenacin的琥珀酸盐,具有抗胆碱能属性的叔胺,用于治疗膀胱过动症的症状。Solifenacin血浆浓度峰值的24.0和40.6 ng / mL达到3 - 8小时后长期口服5或10毫克Solifenacin剂量,分别。在健康成年人的研究显示,这种药物具有较高的绝对生物利用度约为90%,不减少随之而来的食物摄入量。Solifenacin表观分布容积600升,血浆蛋白结合的93 - 96%,而且可能穿过血脑屏障。Solifenacin是消除主要通过肝脏代谢通过细胞色素P450 (CYP) 3 a4,大约只有7%(3 - 13%)剂量的排泄尿液中不变。Solifenacin代谢物不太可能有助于临床Solifenacin效果。在健康成年人,总间隙solifenacin相当于7 - 14 L / h。终端消除半衰期范围从33 85小时,每日一次允许管理。尿排泄在消除solifenacin扮演配角的角色,导致肾清除率的0.67 - -1.51 L / h。CYP1A1/2 Solifenacin不影响活动,2 c9, 2 d6和3 a4,显示了CYP2C19抑制潜在疲软和22体外; however, clinical drug-drug interactions with CYP2C19 and P-glycoprotein substrates are very unlikely. Exposure to solifenacin is increased about 1.2-fold in elderly subjects and about 2-fold in subjects with moderate hepatic and severe renal impairment, as well as by coadministration of the potent CYP3A4 inhibitor ketoconazole 200 mg/day. The full therapeutic effects of solifenacin occur after 2-4 weeks of treatment and are maintained upon long-term therapy. Although solifenacin pharmacokinetics display linearity at doses of 5-40 mg, no obvious dose dependency was observed in efficacy and tolerability studies. The efficacy of solifenacin (5 or 10 mg/day) is at least equal to that of extended-release (ER) tolterodine (4 mg/day) in reducing the mean number of micturitions per 24 hours and urgency episodes, and in increasing the volume voided per micturition. Solifenacin (5 mg/day) appears to be superior to ER tolterodine (4 mg/day) in reducing incontinence episodes (mean -1.30 vs -0.90, p = 0.018) and is superior to propiverine (20 mg/day) at the dose of 10 mg/day in reducing urgency (-2.30 vs -2.78, p = 0.012) and nocturia episodes. Based on withdrawal rates due to adverse effects during the 52-week treatment period, solifenacin appears to have better tolerability than immediate-release (IR) oxybutynin 10-15 mg/day and IR tolterodine 4 mg/day. With regard to the pharmacokinetics of solifenacin, and for safety reasons, doses exceeding 5 mg/day are not recommended for patients with moderate hepatic impairment (Child-Pugh score 7-9), patients with severe renal impairment (creatinine clearance <30 mL/min) and subjects undergoing concomitant therapy with CYP3A4 inhibitors.
DrugBank数据引用了这篇文章
- 药物
- 药物酶
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药物 酶 类 生物 药理作用 行动 Solifenacin 细胞色素P450 1 a1 蛋白质 人类 未知的底物细节 Solifenacin 细胞色素P450 2 d6 蛋白质 人类 未知的底物细节 Solifenacin 细胞色素P450 3 a4 蛋白质 人类 没有底物细节 - 药物载体
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药物 航空公司 类 生物 药理作用 行动 Solifenacin alpha1-acid糖蛋白(蛋白质组) 蛋白质组 人类 未知的粘结剂细节 - 药物反应
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反应 细节 细节 细节 细节
