临床药物动力学的药物用于治疗尿失禁。

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Guay博士

临床药物动力学的药物用于治疗尿失禁。

Pharmacokinet。2003; 42 (14): 1243 - 85。doi: 10.2165 / 00003088-200342140-00004。

PubMed ID
14606931 (在PubMed
]
文摘

急迫性尿失禁(也称为膀胱过动症)是一种常见的尿失禁,单独或作为一个组件的混合发生尿失禁,经常一起应力性尿失禁。病理生理学的急迫性尿失禁,抗胆碱能/止痉挛的代理形式治疗的基石。不幸的是,这些药物的药理作用是不限于尿道,导致系统性不良反应,促进不依从。尽管flavoxate的药物动力学、propantheline莨菪碱,丙咪嗪/去郁敏,trospium氯和propiverine也回顾了这里,只为oxybutynin和tolterodine有足够的疗效/耐受性数据来支持他们的使用在急迫性尿失禁。Oxybutynin吸收较差口服速释片剂配方(2 - 11%)。控释口服制剂显著延长血浆浓度峰值和平均浓度减少波动的程度。大量吸收后发生膀胱内的(膀胱)和皮肤管理,虽然皮肤后主动N-desethyl代谢物的浓度较低与口服相比,可能提高耐受性。食物被发现明显影响的吸收oxybutynin的缓释剂型之一,加强药物释放的速度。Oxybutynin广泛代谢,所以主要是通过去甲基介导的细胞色素P450 (CYP)同工酶。tolterodine的药物代谢动力学情况是在很大程度上依赖CYP2D6的药物基因组学和3 a4同功酶。 In an unselected population, oral bioavailability of tolterodine ranges from 10% to 74% (mean 33%) whereas in CYP2D6 extensive metabolisers and poor metabolisers mean bioavailabilities are 26% and 91%, respectively. Tolterodine is metabolised via CYP2D6 to the active metabolite 5-hydroxymethyl-tolterodine and via CYP3A to N-dealkylated metabolites. Urinary excretion of parent compound plays a minor role in drug disposition. Drug effect is based upon the unbound concentration of the so-called 'active moiety' (sum of tolterodine + 5-hydroxymethyl-tolterodine). Terminal disposition half-lives of tolterodine and 5-hydroxymethyl-tolterodine (in CYP2D6 extensive metabolisers) are 2-3 and 3-4 hours, respectively. Coadministration of antacid essentially converts the extended-release formulation into an immediate-release formulation. Knowledge of the pharmacokinetics of these agents may improve the treatment of urge incontinence by allowing the identification of individuals at high risk for toxicity with 'usual' dosages. In addition, the use of alternative formulations (controlled-release oral, transdermal) may also facilitate adherence, not only by reducing the frequency of drug administration but also by enhancing tolerability by altering the proportions of parent compound and active metabolite in the blood.

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