Tolterodine: Selectivity for the urinary bladder over the eye (as measured by visual accommodation) in healthy volunteers

被引：17

作者：

Chapple C.R. ^{[1
]}

Nilvebrant L. ^{[2
]}

机构：

[1] Department of Urology, The Royal Hallamshire Hospital, Sheffield S10 2JF, Glossop Road

[2] Nilvebrant Plarma Consulting AB, Bromma

来源：

Drugs in R & D | 2002年 / 3卷 / 2期

关键词：

Muscarinic Receptor; Overactive Bladder; Oxybutynin; Tolterodine; Bladder Capacity;

D O I：

10.2165/00126839-200203020-00001

中图分类号：

学科分类号：

摘要：

Objective: Tolterodine exhibits a favourable selectivity for the urinary bladder over salivary glands in vivo, in the anaesthetised cat, whereas oxybutynin shows the opposite selectivity profile in this model. This study further evaluated the selectivity profiles of tolterodine and oxybutynin by comparing the effects on bladder function and visual accommodation in the same individuals. Methods: In a double-blind, randomised, four-way crossover study, 16 healthy volunteers received single oral doses of tolterodine 5mg and oxybutynin 2.5, 5 and 7.5mg. Voiding parameters were assessed for 12 hours post-dose, along with visual accommodation (near point of vision) at regular intervals. Results: A dose-dependent increase in maximum bladder capacity was observed for oxybutynin [2.5mg (+35%), 5mg (+45%) and 7.5mg (+57%)]. The effect of tolterodine 5mg on bladder capacity was approximately twice (+93%) that seen after oxybutynin 5mg and the onset of the effect was more rapid with tolterodine. Effects on visual accommodation were also dose-dependent for oxybutynin (maximum changes in near point of vision were 13%, 20% and 29%, respectively). The maximum change observed after tolterodine 5mg was the same as after oxybutynin 5mg (i.e. 20%). Conclusions: Tolterodine seems to exhibit selectivity for the bladder over the eye. Therefore, these results suggest that the normal dosage of tolterodine (2mg twice daily) may have less effect on visual accommodation than the equivalent dosage of oxybutynin (5mg three times daily) in patients with an overactive bladder.

引用

页码：75 / 81

页数：6

共 32 条

[1]

Wein A.J., Rovner E.S., The overactive bladder: An overview for primary care health providers, Int. J. Fertil Womens Med., 44, pp. 56-66, (1999)

[2]

Nilvebrant L., The mechanism of action of tolterodine, Rev. Contemp. Pharmacother., 11, pp. 13-27, (2000)

[3]

Caulfield M.P., Muscarinic receptors - Characterization, coupling, and function, Pharmacol. Ther., 58, pp. 319-379, (1993)

[4]

Eglen R.M., Hegde S.S., Watson N., Muscarinic receptor subtypes and smooth muscle function, Pharmacol. Rev., 48, pp. 531-556, (1996)

[5]

Caulfield M.P., Birdsall N.J.M., International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors, Pharmacol. Rev., 50, pp. 279-290, (1998)

[6]

Yarker Y.E., Goa K.L., Fitton A., Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability, Drugs Aging, 6, pp. 243-262, (1995)

[7]

Kelleher C.J., Cardozo L.D., Khullar V., Et al., A medium term analysis of the subjective efficacy of treatment for women with detrusor instability and low bladder compliance, Br. J. Obstet. Gynaecol., 104, pp. 988-993, (1997)

[8]

Nilvebrant L., Andersson K.-E., Gillberg P.-G., Et al., Tolterodine -a new bladder selective antimuscarinic agent, Eur. J. Pharmacol., 327, pp. 195-207, (1997)

[9]

Stahl M.M., Ekstirom B., Sparf B., Et al., Urodynamic and other effects of tolterodine: A novel antimuscarinic drug for the treatment of detrusor overactivity, Neurourol. Urodyn., 14, pp. 647-655, (1995)

[10]

Brynne N., Stahl M.M.S., Hallen B., Et al., Pharmacokinetics and pharmacodynamics of tolterodine in man: A new drug for the treatment of urinary bladder overactivity, Int. J. Clin. Pharmacol. Ther., 35, pp. 287-295, (1997)

← 1 2 3 4 →