非索罗定可增加排尿时产生的尿液量，同时减少急迫性尿失禁发作的频率、强度和持续时间[1]。口服摄入后，非特异性酯酶快速、彻底地水解血浆中的非索罗定，产生 Desfesoterodine（5-羟甲基托特罗定；SPM 7605；非索罗定的活性代谢物）[3][4]。

非索罗定（0.01-1 mg/kg；静脉注射）在研究的最低剂量 0.01 mg/kg 下可降低排尿压力并增加膀胱容量和 ICI（间期收缩间隔）[3]。

Animal/Disease Models: Female SD (SD (Sprague-Dawley)) rat bladder (225-275 g) [3]
Doses: 0.01, 0.1 and 1 mg/kg
Route of Administration: intravenous (iv) (iv)injection
Experimental Results: At the lowest dose tested, micturition pressure diminished, bladder Capacity and ICI increased by 0.01 mg/kg.

Absorption, Distribution and Excretion
Tmax (5-HMT): 5 hours post-adminitration of fesoterodine. AUC (0,∞)= 49.5 ng·h/ ml Bioavailability, 5-HMT = 52%
Renal: 70% of fesoterodine was recovered in urine as 5-HMT; 35% carboxy metabolite; 18% carboxy-N-desisopropylmetabolite, and 1% N-desisopropyl metabolite Fecal: 7% Hepatic: fesoterodine elimination via CYP2D6 and CYP3A4
IV, 5-HMT: 169 L
5-HMT, healthy subjects: 14.4 L/h 5-HMT is also secreted into the nephron.

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Metabolism / Metabolites
Metabolized by ubiquitous, nonspecific esterases to transform fesoterodine into 5-HMT Extensive metabolism via CYP2D6 and CYP3A4 into inactive metabolites

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Biological Half-Life
7-8 hours for the active metabolite 5-hydroxymethyl tolterodine

Hepatotoxicity
Like most anticholinergic agents, fesoterodine has not been linked to episodes of liver enzyme elevations or clinically apparent liver injury. In prospective, randomized, placebo-controlled trials of fesoterodine in overactive bladder syndrome, serum aminotransferase elevations were rare, arising in less than 1% of recipients, rates similar to those in placebo recipients. Since its approval, there have been no published case reports of clinically apparent liver injury attributed to fesoterodine.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of fesoterodine during breastfeeding. Long-term use of fesoterodine might reduce milk production or milk letdown. During long-term use, observe for signs of decreased lactation (e.g., insatiety, poor weight gain).
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information in nursing mothers was not found as of the revision date. Anticholinergics can inhibit lactation in animals apparently by inhibiting growth hormone and oxytocin secretion. Anticholinergic drugs can also reduce serum prolactin in nonnursing women. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Protein Binding
5-HMT: 50% to albumin and alpha1-acid glycoprotein

[1]. Fesoterodine for the treatment of urinary incontinence and overactive bladder. Ther Clin Risk Manag. 2009;5:869-76. Epub 2009 Nov 18.

[2]. The Beneficial Effect of Fesoterodine, a Competitive Muscarinic Receptor Antagonist on Erectile Dysfunction in Streptozotocin-induced Diabetic Rats.

[3]. Pharmacological Characterization of a Novel Investigational Antimuscarinic Drug, Fesoterodine, in Vitro and in Vivo. BJU Int. 2008 Apr;101(8):1036-42.

[4]. Fesoterodine: A Novel Muscarinic Receptor Antagonist for the Treatment of Overactive Bladder Syndrome. Expert Opin Pharmacother. 2008 Jul;9(10):1787-96.

Fesoterodine is a diarylmethane.
Fesoterodine is an antimuscarinic prodrug for the treatment of overactive bladder syndrome.
Fesoterodine is an anticholinergic and antispasmotic agent used to treat urinary incontinence and overactive bladder syndrome. Fesoterodine has not been implicated in causing liver enzyme elevations or clinically apparent acute liver injury.
Fesoterodine is a competitive muscarinic receptor antagonist with muscle relaxant and urinary antispasmodic properties. Fesoterodine is rapidly hydrolyzed in vivo into its active metabolite 5-hydroxy methyl tolterodine, which binds and inhibits muscarinic receptors on the bladder detrusor muscle, thereby preventing bladder contractions or spasms caused by acetylcholine. This results in the relaxation of bladder smooth muscle and greater bladder capacity, in addition to a reduction in involuntary muscle contractions and involuntary loss of urine. The active metabolite does not interact with alpha-adrenergic, serotonergic, histaminergic and excitatory amino acid receptors and is eliminated via renal excretion.
See also: Fesoterodine Fumarate (has salt form).

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Drug Indication
Fesoterodine is indicated for the treatment of overactive bladder in adult patients with symptoms of urge urinary incontinence, urgency, and frequency. It is also indicated in the treatment of neurogenic detrusor overactivity in pediatric patients ≥6 years old weighing >25 kg.
FDA Label
Treatment of the symptoms (increased urinary frequency and / or urgency and / or urgency incontinence) that may occur in patients with overactive-bladder syndrome.

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Mechanism of Action
Fesoterodine, once converted to its active metabolite, 5-hydroxymethyltolterodine, acts as a competitive antagonists at muscarinic receptors. This results in the inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder.

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Pharmacodynamics
In-vivo the fesoteridine prodrug is broken down into its active metabolite, 5-hydroxymethyl tolterodine (5-HMT), by plasma esterases. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. Therefore, acting as a competitive muscarinic receptor antagonist, fesoterodine ultimately acts to decrease the detrusor pressure by its muscarinic antagonism, thereby decreasing bladder contraction and consequently, the urge to urinate.

C26H37NO3

411.5769

412.285

286930-02-7

Fesoterodine L-mandelate;1206695-46-6;Fesoterodine fumarate;286930-03-8

6918558

Colorless to light yellow viscous liquid

1.043

518.9ºC at 760 mmHg

267.6ºC

5.488

49.77

1

4

11

30

491

1

O(C(C([H])(C([H])([H])[H])C([H])([H])[H])=O)C1C([H])=C([H])C(C([H])([H])O[H])=C([H])C=1[C@@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C([H])([H])C([H])([H])N(C([H])(C([H])([H])[H])C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])[H]

DCCSDBARQIPTGU-HSZRJFAPSA-N

InChI=1S/C26H37NO3/c1-18(2)26(29)30-25-13-12-21(17-28)16-24(25)23(22-10-8-7-9-11-22)14-15-27(19(3)4)20(5)6/h7-13,16,18-20,23,28H,14-15,17H2,1-6H3/t23-/m1/s1

[2-[(1R)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methylpropanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。  (2). 该产品在溶液状态不稳定，请现配现用。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~242.97 mM)
Ethanol : ~50 mg/mL (~121.48 mM)

配方 1 中的溶解度: ≥ 2.75 mg/mL (6.68 mM) (饱和度未知) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 27.5 mg/mL的澄清EtOH储备液加入到400 μL PEG300中并混合均匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.75 mg/mL (6.68 mM) (饱和度未知) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 27.5 mg/mL 澄清乙醇储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.75 mg/mL (6.68 mM) (饱和度未知) in 10% EtOH + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 27.5 mg/mL 澄清 EtOH 储备液添加到 900 μL 玉米油中并充分混合。

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配方 4 中的溶解度: ≥ 2.5 mg/mL (6.07 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清的 DMSO 储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL 生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 2.5 mg/mL (6.07 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
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