Detrol
[Treatment of bladder instability (non-neurogenic hyperactive bladder) in children, with tolterodine]

[Article in Spanish]

Garat Barredo JM, Caffaratti Sfulcini J, de la Pena E.

Unidad de Urologia Pediatrica, Servicio de Urologia, Fundacio Puigvert, Barcelona.

INTRODUCTION: Overactive bladder (OB) is one of the no-neurogenic voiding dysfunctions whose prevalence has been precisely defined among the general population but not so among the paediatric population. Its clinical manifestations are various, and its association with other pathologies like enuresis, vesico-ureteral reflux (VUR) and recurrent infections is particularly significant in children. OB is basically managed with anticholinergic drugs. The efficacy of oxybutynin chloride has been sufficiently proved; however its dosage and side effects, although scarce in children, usually cause treatment discontinuation. OBJECTIVES: Tolterodine has been successfully used as an alternative therapy of OB in adults, however its use has not been sufficiently evaluated in children. Our objective is to determine tolterodine's efficacy and tolerability in the paediatric population suffering from OB. MATERIAL AND METHODS: A retrospective study of 72 children who were diagnosed no-neurogenic OB and who received no previous treatment. A concomitant urological pathology diagnostic protocol was applied to all cases, as well as a urodynamic test (UDT) and a neurological examination. Post-treatment UDT was performed to one group of patients. RESULTS: The mean age was 10.9 years and the children were assessed between 4 and 31 months after treatment initiation. Healing was proved through cistomanometry in 67% of the cases, there was improvement in 14% and 19% of the patients showed no changes in the UDT. Following the criteria of the International Children's Continence Society (ICCS) applied to those children with no post-treatment UDT, 51% were healed, 27% improved and 22% experienced no changes. None of the patients had to discontinue the treatment due to side effects. CONCLUSIONS: Tolterodine's tolerability and efficacy are good within the paediatric population, which turns it into an alternative to the traditional anticholinergics for the treatment of OB.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15074060&dopt=Abstract tolterodine Detrol



Detrol
Canadian economic comparison of extended-release oxybutynin and immediate-release tolterodine in the treatment of overactive bladder.

Getsios D, Caro JJ, Ishak KJ, El-Hadi W, Payne K.

Caro Research Institute, Hammonds Plains, Nova Scotia, Canada.

BACKGROUND: Overactive bladder (OAB) is a condition characterized by urgency, increased frequency of micturition, or urge incontinence. It affects a considerable segment of the population, particularly with increasing age. Pharmacotherapy is one of the most common approaches to the treatment of OAB. OBJECTIVE: This article describes the development and results of a model comparing health-economic outcomes for the new extended-release (XL) formulation of oxybutynin and immediate-release (IR) tolterodine in a population of community-dwelling Canadian adults with OAB. METHODS: A Markov model was developed to compare health-economic outcomes over the course of 1 year. Effectiveness and treatment-persistence data were derived from the OBJECT (Overactive Bladder: Judging Effective Control and Treatment) trial, a 3-month comparison of oxybutynin XL 10 mg and tolterodine IR 4 mg, and were used, together with data from the literature (identified through a MEDLINE search of articles published between 1990 and 2003), to project outcomes beyond the trial period. Severity-specific cost profiles for incontinence were developed. In the principal analyses, cost items were limited to drug therapy, physician visits, use of pads or other protection, and laundry costs. Costs are reported in 2002 Canadian dollars. RESULTS: Costs after 1 year were estimated to be an average of $32 less per patient for oxybutynin XL compared with tolterodine IR, and 3.1 additional patients in every 100 who received oxybutynin XL were expected to attain complete continence compared with those who received tolterodine. During the course of 1 year, patients receiving oxybutynin XL were expected to have a mean 16.5 additional incontinence-free days compared with those receiving tolterodine IR. The results were sensitive to relative drug prices. In the other sensitivity analyses, however, oxybutyrin XL maintained its advantage over a wide range of inputs. CONCLUSION: The results of these analyses suggest that when priced equivalently, oxybutynin XL would reduce costs and provide better results than tolterodine IR over 1 year of treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15110136&dopt=Abstract tolterodine Detrol



Detrol
Functional selectivity of muscarinic receptor antagonists for inhibition of M3-mediated phosphoinositide responses in guinea pig urinary bladder and submandibular salivary gland.

Nelson CP, Gupta P, Napier CM, Nahorski SR, Challiss RA.

Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester, LE1 9HN, UK.

Binding and functional affinities of the muscarinic acetylcholine (mACh) receptor antagonists darifenacin, tolterodine, oxybutynin, and atropine were assessed in Chinese hamster ovary (CHO) cells expressing the human recombinant M2 (CHO-m2) or M3 (CHO-m3) receptors, and in guinea pig bladder and submandibular gland. In [N-methyl-3H]scopolamine methyl chloride binding studies in CHO cells, darifenacin displayed selectivity (14.8-fold) for the M3 versus M2 mACh receptor subtype. Oxybutynin was nonselective, whereas atropine and tolterodine were weakly M2-selective (5.1- and 6.6-fold, respectively). Antagonist functional affinity estimates were determined by the inhibition of agonist-induced [3H]inositol phosphate accumulation in CHO-m3 cells and antagonism of the agonist-induced inhibition of forskolin-stimulated cyclic AMP accumulation in CHO-m2 cells. Darifenacin was the most M3-selective antagonist (32.4-fold), whereas oxybutynin, atropine, and tolterodine exhibited lesser selectivity. Functional affinity estimates in guinea pig urinary bladder and submandibular salivary gland using indices of phosphoinositide turnover revealed that oxybutynin, darifenacin, and tolterodine each displayed selectivity for the response in the bladder, relative to that seen in the submandibular gland (9.3-, 7.9-, and 7.4-fold, respectively). In contrast, atropine displayed a similar affinity in both tissues. These data demonstrate that in bladder, compared with submandibular gland from a single species, the mACh receptor antagonists darifenacin, tolterodine, and oxybutynin display selectivity to inhibit agonist-mediated phosphoinositide responses. It is proposed that both responses are mediated via M3 mACh receptor activation and that differential functional affinities displayed by some, but not all, antagonists are indicative of the influence of cell background upon the pharmacology of the M3 mACh receptor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15140916&dopt=Abstract tolterodine Detrol



Detrol
In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats.

Ohtake A, Ukai M, Hatanaka T, Kobayashi S, Ikeda K, Sato S, Miyata K, Sasamata M.

Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan. ohtake yamanouchi.co.jp

Solifenacin succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the in vitro and in vivo bladder selectivity profile of solifenacin over salivary gland in the same animal species, and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin and atropine. Solifenacin and the other antimuscarinic drugs inhibited carbachol-induced increases in intracellular Ca(2+) levels in bladder smooth muscle cells and salivary gland cells isolated from rats in a concentration-dependent manner. The inhibitory effect of solifenacin for bladder smooth muscle cells (pK(i)=8.12) was 3.6-fold more potent than that for salivary gland cells (pK(i)=7.57). In contrast, the inhibitory effects of the other antimuscarinic drugs for bladder smooth muscle cells were 1.7- to 2.2-fold more potent than those for salivary gland cells. In anesthetized rats, solifenacin dose-dependently inhibited carbachol-induced intravesical pressure elevation and salivary secretion, and exhibited functional selectivity (3.7- to 6.5-fold) for urinary bladder over salivary gland. Tolterodine was also 2.2- to 2.4-fold more selective in inhibition of bladder response. In contrast, oxybutynin, darifenacin and atropine did not show functional selectivity for urinary bladder. These results indicate that solifenacin exerts greater selectivity for urinary bladder over salivary gland than tolterodine, oxybutynin, darifenacin and atropine, and may consequently provide symptomatic benefit in the treatment of overactive bladder with less dry mouth than currently used antimuscarinic drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15178371&dopt=Abstract tolterodine Detrol