Oxybutynin gel for the treatment of overactive bladder

Benign prostatic hyperplasia is an increasingly prevalent condition affecting > 50% of men > 65 years of age. Although it is a condition that is unlikely to be life threatening, it can significantly affect quality of life with distressing lower urinary tract symptoms. Increasingly, medical therapy is being used as first-line treatment for men with moderate-to-severe lower urinary tract symptoms. Two main pharmacological classes of drugs are used: 5α-reductase inhibitors and α-1 selective blockers. Both these classes of drugs have shown good tolerability and clinical efficacy. This article examines the potential benefit of the use of combination therapy. In particular, what is the evidence for using doxazosin and finasteride therapy together?     

盐酸奥昔布宁醇脂质体凝胶的制备及质量评 价简

目的 制备盐酸奥昔布宁醇脂质体凝胶剂,并评价体外经皮渗透性、pH、外观形态等方面的质量.方法 以羟丙基纤维素（HPC）为基质制备OXB醇脂质体凝胶;采用Franz透皮扩散实验仪考察醇脂质体凝胶和普通凝胶的经皮渗透性;高效液相色谱法测定其中主药含量,并评价其质量.结果 醇脂质体凝胶（4％ OXB）的累积渗透率是普通凝胶（10％ OXB）的3.9倍.盐酸奥昔布宁线性范围为10 ～1 000 μg/mL,平均回收率为99.58％.结论 制备的醇脂质体凝胶经皮渗透性高,质量稳定可控.     

The anticholinergic drug oxybutynin inhibits voltage‐dependent K+ channels in coronary arterial smooth muscle cells

This study demonstrates the inhibitory effect of anticholinergic drug oxybutynin on voltage‐dependent K⁺ (Kv) channels in rabbit coronary arterial smooth muscle cells. Oxybutynin inhibited vascular Kv channels in a concentration‐dependent manner, with an IC₅₀ value of 11.51 ± 0.38 μmol/L and a Hill coefficient (n) of 2.25 ± 0.12. Application of oxybutynin shifted the activation curve to the right and the inactivation curve to the left. Pretreatment with the Kv1.5 subtype inhibitor DPO‐1 and the Kv2.1 subtype inhibitor guangxitoxin suppressed the oxybutynin‐induced inhibition of the Kv current. However, application of the Kv7 subtype inhibitor linopirdine did not affect the inhibition by oxybutynin of the Kv current. The anticholinergic drug atropine did not inhibit the Kv current nor influence oxybutynin‐induced inhibition of the Kv current. From these results, we concluded that oxybutynin inhibited the vascular Kv current in a concentration‐dependent manner by influencing the steady‐state activation and inactivation curves independent of its anticholinergic effect.     

托特罗定治疗特发性膀胱过度活动症

目的观察新型毒蕈咸受体拮抗药托特罗定治疗特发性膀胱过度活动症的有效性和安全性。方法将托特罗定1mg呼奥昔布宁5mg及安慰剂进行对比,疗程3周。夜间入睡前2h口服。结果与安慰剂相比,托特罗定和奥昔布宁都使入睡前1h夜尿次数(P<0.01)显著减少。两种药物的副作用主要为口干。在口干(发生率和强度)方面,托特罗定要明显优于奥昔布宁(P<0.05)。结论托特罗定治疗特发性膀胱过度活动症效果明确,疗程3周即能达到疗效。尽管奥昔布宁也具有很好的疗效,但不良反应限制了它的应用。     

奥昔布宁渗透泵控释片在犬体内的单剂量和多剂量生物等效性研究

 目的研究自制奥昔布宁渗透泵控释片与市售普通片以及进口控释片在犬体内的单剂量和多剂量生物等效性。方法利用液相-质谱检测血药浓度,采用随机、交叉实验设计对自制控释片、进口控释片和市售普通片进行对照研究。结果单剂量给药后奥昔布宁自制控释片、进口控释片和市售普通片的峰浓度(ρ_max)、达峰时间(t_max)、血药浓度曲线下面积AUC分别为:(1.77±0.51),(1.67±0.27)和(5.89±2.04)μg·L^-1,(10.00±2.14),(10.50±2.07)和(0.84±0.23)h,(50.69±11.83),(48.63±6.33)和(22.74±7.06)μg·h·L^-1。多剂量给药后分别为:(2.39±0.55),(2.07±0.41)和(7.80±1.56)μg·L^-1,(6.12±1.55),(8.12±1.88)和(0.62±0.19)h,(44.92±10.63),(41.50±9.05)和(21.92±4.37)μg·h·L^-1,达稳态时血药浓度波动系数(DF)分别为(0.76±0.17),(0.52±0.17)和(2.55±0.39)。结论经方差分析和双单侧t检验,自制片与进口片和普通片生物等效。     

The use of tolterodine in children after oxybutynin failure

OBJECTIVE: To assess the safety and efficacy of tolterodine tartrate prescribed to children who previously failed to tolerate oxybutynin chloride. PATIENTS AND METHODS: We reviewed 34 children, followed for>1 year, who were prospectively crossed-over from oxybutynin to tolterodine because of side-effects. The initial diagnosis was dysfunctional voiding in 31 patients. All patients were placed on a behavioural modification protocol. When their symptoms did not improve after 6 months, treatment with an anticholinergic agent was considered. Urodynamic studies were conducted in 20 patients, confirming uninhibited contractions in 19. The remaining 14 patients were empirically started on antimuscarinic or anticholinergic agents. The 34 patients were treated with oxybutynin for a median (range) of 6 (2-84) months. When significant side-effects were reported, they were crossed over to tolterodine. The efficacy of tolterodine was assessed as defined by the International Children's Continence Society, with tolerability assessed and side-effects documented using a questionnaire. RESULTS: The mean age at the first dose of tolterodine was 8.9 years; the dose was 1 mg twice daily for 12 patients and 2 mg twice daily for 22. The median treatment with tolterodine was 11.5 months, with 20 (59%) patients reporting no side-effects; six described the same but tolerable side-effects as with oxybutynin. Eight patients discontinued tolterodine because of side-effects after a median (range) of 5 (1-11) months. The efficacy of tolterodine was comparable with that of oxybutynin, as reported by the questionnaire and voiding diaries. The reduction in wetting episodes at 1 year was> 90% in 23 (68%), more than half in five and less than half (or failure) in six patients. CONCLUSION: Tolterodine is tolerated well in children. In this subgroup of patients who could not tolerate oxybutynin, 77% were able to continue tolterodine treatment with no significant side-effects.     

Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers

Purpose. To characterize the enantiomers of oxybutynin (OXY) and N-desethyloxybutynin (DEO) following transdermal and oral administration. Methods. OXY was administered either as a single transdermal system over a 96 h wear period or as a single 5 mg immediate-release tablet to 18 healthy male and female subjects in a randomized, open-label, two-way crossover design. Blood samples were collected for 108 h after application of the transdermal system and for 6 h after oral administration. Plasma concentrations of the R- and S-enantiomers of OXY and DEO were assayed by LC-MS/MS. Enantiomer in vitro skin flux was evaluated using human cadaver skin.Results. In vitro skin flux studies demonstrated equal absorption of R and S- OXY. Plasma concentrations and pharmacokinetic parameters of the R-enantiomers of OXY and DEO were slightly lower than the S-enantiomers following transdermal OXY. The relative AUC values were S-OXY>S-DEO>R-OXY>R-DEO. The AUC ratios of DEO/OXY were less than 1 for both the R- and S- enantiomers. Following oral dosing, plasma DEO concentrations greatly exceeded OXY resulting in relative AUC values of R-DEO>S-DEO>S-OXY>R-OXY. The mean AUC ratios of S- and R-DEO/OXY were 3.25 and 8.93, respectively. Conclusions. Stereoselective metabolism of OXY was evident following both transdermal and oral administration of OXY. The reduced pre-systemic metabolism of transdermally administered OXY compared to oral administration resulted in not only significantly lower DEO plasma concentrations, but also a different metabolite pattern. The differences between R-OXY and R-DEO following the two routes of administration support the potential for comparable clinical efficacy and reduced anticholinergic side-effects with transdermal treatment.     

奥昔布宁对映体的高效毛细管电泳拆分

目的：建立一种快捷的高效毛细管电泳法对奥昔布宁对映体进行手性拆分。方法：分别考察了运行缓冲液的溶质浓度和pH值、手性选择剂的种类和浓度,以及分离电压大小对奥昔布宁外消旋体分离度的影响。结果：确定最佳分离条件为：运行缓冲液为含5％磺化-β-环糊精的20mmol·L-1磷酸溶液,以三乙醇胺调节其pH为3．0,分离电压为-30kV,柱温为16℃。在此条件下,奥昔布宁可获得良好分离,分离度为2．6,分离时间小于6min。结论：该法简便可行,可迅速对奥昔布宁对映体进行拆分。     

INTRAVESICAL THERAPY FOR THE TREATMENT OF NEUROGENIC BLADDER IN CHILDREN

Background : Oral pharmacotherapy has been commonly used as an adjunct to clean intermittent catheterization (CIC) in the treatment of neurogenic bladder in order to achieve continence, but may be associated with unacceptable side effects. The authors' experience with sterile intravesical preparations of oxybutynin hydrochloride and ephedrine in children is reported here. Methods : Patients requiring CIC for neurogenic bladder but with incontinence that was unresponsive to standard oral therapy or that was associated with severe systemic side effects were studied over a 1-year period. Clinical, radiological and urodynamic assessments were made prior to commencing treatment with intravesical oxybutynin hydrochloride. Patients who remained incontinent with poor internal sphincter muscle tone had intravesical ephedrine added. Results : Seven patients were involved in the study over a 1-year period. Two patients became continent and one patient had an improvement in upper tract dilatation. One patient had a limited improvement with oxybutynin alone but became continent with the addition of ephedrine. Three patients had no response to treatment. There were few side effects. Conclusion : Intravesical agents have a role in the management of paediatric neurogenic bladder for those children with significant adverse sequelae from oral pharmacotherapy who would otherwise require surgical intervention. Intravesical therapy is a safe technique in children with sterile preparations. Further investigation of this modality should be pursued.