Disease relevance of Oxytrol

• Oxybutynin for diabetic complications [1].
• By combining the dose-urge urinary incontinence and dose-dry mouth relationship, a wider therapeutic index was predicted for oxybutynin XL than for immediate-release oxybutynin [2].
• Hyperhidrosis and hypothermia responsive to oxybutynin [3].
• Inhibition of hyperreflexia by vaginally administered oxybutynin: a novel rabbit model [4].
• Oxybutynin lowers elevated renal pelvic pressures in a rat congenital unilateral hydronephrosis [5].

Psychiatry related information on Oxytrol

• The renal and bladder related characteristics of children with monosymptomatic enuresis responsive to oxybutynin were evaluated [6].
• PURPOSE: To improve patient compliance with and acceptance of intravesical oxybutynin therapy for neurogenic bladder dysfunction we developed a stable oxybutynin solution that eliminates the complicated crushing procedure [7].
• However, we observed lower baseline cognitive functioning in patients whose parents chose oxybutynin over behavior modification alone [8].
• CONCLUSION: Individuals aged > or = 50 years had a more distinct impairment of REM sleep after oxybutynin and tolterodine than had young people, but the reduction in REM sleep did not reach a pathological degree in this single-dose study [9].
• Psychotic disorder induced by oxybutynin: Presentation of two cases [10].

High impact information on Oxytrol

• In this study we determined whether pH has an effect on drug release from the ER formulations of oxybutynin (OROS technology) and tolterodine (membrane coated beads) in vitro and in vivo [11].
• Direct comparative studies in patients with overactive bladder indicate that trospium chloride is at least as effective as oxybutynin and tolterodine [12].
• Effect of antacid on the pharmacokinetics of extended-release formulations of tolterodine and oxybutynin [11].
• The OROS-based oxybutynin extended-release (ER) formulation (Lyrinel XL; Ditropan XL) represents a new form of oral delivery for oxybutynin, a muscarinic receptor antagonist used in the treatment of overactive bladder (OAB) [13].
• Oxybutynin is extensively metabolised, principally via N-demethylation mediated by the cytochrome P450 (CYP) 3A isozyme [14].

Chemical compound and disease context of Oxytrol

• Tolterodine: superior tolerability than and comparable efficacy to oxybutynin in individuals 50 years old or older with overactive bladder: a randomized controlled trial [15].
• Comparative evaluation of central muscarinic receptor binding activity by oxybutynin, tolterodine and darifenacin used to treat overactive bladder [16].
• PURPOSE: We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis [17].
• CONCLUSIONS: Vaginally delivered oxybutynin was effective in improving bladder compliance, inhibiting intra-arterial Ach stimulated bladder contractions and significantly decreasing the amplitude of hyperreflexia [4].
• Our results indicate that oxybutynin is more effective than propantheline in the treatment of detrusor hyperreflexia in patients with multiple sclerosis [18].

Biological context of Oxytrol

• It is as potent as oxybutynin in inhibiting bladder contraction, but is much less potent in inhibiting salivation, suggesting that it may have less propensity to cause dry mouth in clinical use [19].
• These patients were compared to those not using oxybutynin with regard to urodynamic parameters and upper tract deterioration [20].
• CONCLUSIONS: Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration [21].
• The ratio for the AUC values for N-desethyl-oxybutynin and oxybutynin was 2.1 +/- 0.2 (n = 11) [22].
• CONCLUSIONS: Oxybutynin, a commonly used pharmacological agent in pediatric urology, was not associated with cognitive impairment following treatment [8].

Anatomical context of Oxytrol

• We report a case of improved function of a previously poorly complaint gastric neobladder caused by oxybutynin, thereby demonstrating a direct action on gastric smooth muscle [23].
• At 1 and 3 h after oral administration of oxybutynin, there was a significant increase in apparent dissociation constant (Kd) for specific [N-methyl-3H]scopolamine ([3H]NMS) binding in the rat bladder, submaxillary gland, heart, and colon compared with control values [24].
• The role of oxybutynin in spinal cord injured patients with indwelling catheters [20].
• Indeed, when rats with urinary tract infection were treated with oxybutynin, their renal pelvic pressures were lower than those in uninfected rats [25].
• CONCLUSIONS: Intravesical oxybutynin in rats may cause selective binding of bladder muscarinic receptors via a direct local effect, while oral oxybutynin may exert predominant binding of salivary gland receptors [26].

Associations of Oxytrol with other chemical compounds

• CONCLUSIONS: Untoward effects and inconvenience are the most common reasons for discontinuing intravesical oxybutynin chloride therapy for neurogenic bladder dysfunction [27].
• Oral administration of oxybutynin (76.1 micromol/kg), tolterodine (6.31 micromol/kg) and darifenacin (59.1 micromol/kg) showed binding activity that was approximately equal to that of bladder muscarinic receptors [16].
• Consequently tolterodine, 5-HM and DPr-P-4(N-->O) compared with oxybutynin, DEOB, propiverine and darifenacin were found to show 3 to 4 times greater affinity to muscarinic receptors in the human bladder than in the parotid gland [28].
• Moreover, intravesical oxybutynin had little muscarinic receptor binding activity in the heart and colon, and little significant suppression of pilocarpine induced salivation in rats [26].
• 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) [29].

Gene context of Oxytrol

• Recombinant CYP3A5 enzyme had higher activity in oxybutynin N-deethylation than recombinant CYP3A4 [30].
• Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs [31].
• EMDA of oxybutynin reduced detrusor hyperreflexia [32].
• Effects of oxybutynin on vesicoureteral reflux in children [33].
• 3 Plasma concentrations of oxybutynin and its active metabolite (N-desethyl-oxybutynin, DEOB) were maximum 0.5 h after its oral administration and then declined rapidly [34].

Analytical, diagnostic and therapeutic context of Oxytrol

• Oxybutynin XL efficacy and side-effect data obtained from two parallel-group, randomized, controlled clinical trials were modeled to evaluate the therapeutic index [2].
• Hence, given its overall efficacy/tolerability profile and dosage flexibility, oxybutynin ER provides an excellent treatment option in the first-line pharmacotherapy of OAB [13].
• In two randomised, double-blind studies in patients with OAB, the improvement in all the symptoms with once-daily oxybutynin ER 5-30 mg/day was similar to that produced by oxybutynin IR 5-20 mg/day given one to four times daily [13].
• Intravesical instillation (0.2 mg./kg./dose), on the other hand, resulted in reduced metabolite generation and peak plasma concentrations for N-desethyl-oxybutynin which were in the same range as those for oxybutynin, the ratio being 1.2 +/- 0.1 (n = 11) [22].
• Oral administration of oxybutynin (76.1 micromol/kg) showed significant binding of cerebral cortical muscarinic receptors in mice, as indicated by about a 2-fold increase in K(d) values for specific [(3)H]N-methylscopolamine binding 0.5 and 2 hours later [16].

References