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Polymeric drug-releasing vaginal rings are useful for both local and systemic administration of drugs via the intravaginal route. Typically, they provide continuous sustained or controlled release of drug(s) over extended time periods, thereby avoiding overdose and improving adherence. This first-in-human study (EudraCT number: 2020-0050044-30) evaluated the pharmacokinetics, safety, and tolerability of a single dose of oxybutynin administered by a novel microprocessor-controlled vaginal ring (MedRing). Eight healthy female subjects received an electronically controlled single intravaginal dose of 3 mg oxybutynin hydrochloride (100 mg/mL) dissolved in 1:1 water/propylene glycol administered via MedRing. Following dosing, MedRing was kept in situ for up to 6 h. Blood samples were collected 1 h prior to oxybutynin dosing and subsequently at regular intervals post-dose for the assessment of plasma concentrations of oxybutynin and its active metabolite N-desethyloxybutynin. The results showed that MedRing efficiently administered oxybutynin via the intravaginal route, resulting in plasma oxybutynin levels comparable to orally administered oxybutynin. The mean ± standard deviation pharmacokinetic parameters for oxybutynin were Cmax 5.4 ± 2.7 ng/mL, AUCinf 34.9 ± 17.4 h ng/mL, t1/2 8.5 ± 3.5 h and for N-desethyloxybutynin were Cmax 3.9 ± 2.5 ng/mL, AUCinf 51.1 ± 43.1 h ng/mL, t1/2 7.7 ± 5.9 h. No serious adverse events were reported. The study demonstrates that intravaginal administration of oxybutynin hydrochloride using the MedRing device was well tolerated.

According to class M2.1 of the World Anti-Doping Agency (WADA) Prohibited List, the manipulation of doping control urine samples to alter their integrity and validity is prohibited both in- and out-of-competition. However, some paraplegic athletes with an overactive bladder need to be regularly treated with anti-cholinergic and anti-spasmodic drugs such as oxybutynin, which are often administered intravesically to reduce the substantial side effects observed after oral application. So far, it remains unclear whether such bladder instillations have a negative impact on analytical procedures and thus represent an anti-doping rule violation. Within this pilot study, urine samples were collected from five paraplegic athletes before and after an intravesical oxybutynin hydrochloride instillation. The samples were routinely tested for the presence of performance-enhancing drugs and afterwards fortified with 25 model compounds representing different classes of doping agents (anabolic agents, cannabinoids, diuretics, glucocorticoids, hormone and metabolic modulators, and stimulants) at low and medium concentrations. Additionally, the pH value and specific gravity were measured and the presence of oxybutynin was qualitatively determined by gas chromatography-mass spectrometry (GC-MS). In initial testing procedures, all samples were tested negative. Oxybutynin was present in most of the samples but found to have no significant effect on the detectability of the 25 model compounds subsequently added to each urine specimen. Therefore, it can be concluded that intravesical instillations with oxybutynin hydrochloride do not alter the integrity and validity of doping control urine samples.

Hyperhidrosis (HH) is characterized by sweating exceeding the amount necessary to meet the thermal regulation and physiological needs of the body. Approximately 9.41% of individuals with HH have craniofacial hyperhidrosis (FH). The present study aims to review the most current data in the literature regarding craniofacial hyperhidrosis, including pathophysiology, diagnosis and clinical presentation, treatment options (clinical and surgical), and outcomes. VATS (videothoracoscopy sympathectomy) is considered the gold standard for definitive treatment of axillary or palmar hyperhidrosis. Recently, several studies have shown the usefulness of clinical treatment with oxybutynin hydrochloride, leading to clinical improvement of HH in more than 70% of users. Both clinical and surgical treatment of craniofacial hyperhidrosis have good results. However, surgical treatment of FH is associated with more complications. Clinical treatment with oxybutynin hydrochloride yields good results and can be the first therapeutic option. When the patient is not satisfied with this treatment and has good clinical conditions, surgical treatment can be used safely. Resumo A hiperidrose (HH) é caracterizada por transpiração além da quantidade necessária para manter a regulação térmica e as necessidades fisiológicas do corpo. Aproximadamente 9,41% dos indivíduos com HH apresentam hiperidrose craniofacial (FH). Este estudo tem como objetivo revisar os dados mais atuais da literatura sobre FH, incluindo fisiopatologia, diagnóstico e apresentação clínica, opções de tratamento (clínico e cirúrgico) e desfechos. A simpatectomia por videotoracoscopia (VATS) é considerada o padrão-ouro para o tratamento definitivo da hiperidrose axilar ou palmar. Recentemente, vários estudos demonstraram a utilidade do tratamento clínico com cloridrato de oxibutinina, que leva à melhora clínica da HH em mais de 70% dos pacientes. O tratamento clínico e o cirúrgico apresentam bons resultados no tratamento da FH. No entanto, o tratamento cirúrgico da FH apresenta mais complicações. O tratamento clínico com cloridrato de oxibutinina fornece bons resultados e pode ser a primeira opção terapêutica. Quando o paciente não está satisfeito com esse tratamento e mostra boas condições clínicas, o tratamento cirúrgico pode ser usado com segurança.

Oxybutynin hydrochloride (OB) is often used in intravesical instillation therapy for spastic neurogenetic bladder.The purposeof this study was to determine the expiration date and administration device for intravesically administered OB solutionscontaining sodium hyaluronate (HYA) as a pharmaceutical additive to enhance the muco-adhesiveness of the solution.The stability of OB in containers made of glass,polystyrene (PS),polypropylene (PP) and polyethylene (PE) was investigatedunder various temperature and light exposure conditions.Sorption of OB was observed in PP and PE containers andfor the latter,it was enhanced at higher temperatures and pHs.Based on these results,the optimal expiration date and storageconditions of OB solution were determined to be 84 days in a cool place (4°C),in a PP container.

Intravesical oxybutynin hydrochloride was administered to 17 patients with a neuropathic bladder (myelomeningocele in 15 and spinal cord tumour in two) and urinary incontinence refractory to intermittent catheterisation. Therapy consisted of instillation of a 10 ml solution containing 5 mg oxybutynin hydrochloride twice daily. The cystometric bladder capacity before and after 1 hour of intravesical oxybutynin hydrochloride was 132 +/- 45 ml and 193 +/- 71 ml (mean +/- 1 standard deviation, p0.01) in all 17 patients. In 13 patients with low compliant bladders, the mean bladder compliance before and after 1 hour of instillation was 4.2 +/- 2.4 ml/cmH2O and 8.5 +/- 6.4 ml/cmH2O respectively (p0.01). The period of the intravesical oxybutynin hydrochloride treatment ranged from 2 to 16 months (mean 11.1 months). The improvement rate of 'moderately improved' and better response was 76.5% in all 17 patients. One patient complained of slight lower abdominal pain, which receded as treatment continued. Since the pH value of the solution appeared to be so low as to irritate the vesical mucosa, the value was adjusted to 5.85. No local or systemic side effects were observed thereafter. These encouraging results suggest that intravesical instillation of oxybutynin hydrochloride is an attractive alternative in patients with a neuropathic bladder, who are either unresponsive to or have intolerable side effects from oral medications.

神経因性膀胱をはじめとして頻尿, 尿意切迫感および尿失禁を主訴とする患者を対象として塩酸オキシブチニンを投与し, 臨床症状を中心にその有効性, 安全性につき検討した.1)総症例数52例中44例が4週以上の投与を完了した.平均投与期間は66.8日であった.2)投与量別全般改善度を評価した成績は2 mg×3回群で"改善"以上の改善率は55%, "やや改善"以上が85%であり, 3 mg×3回群でそれぞれ68.2%, 95.5%であった.また1日2回投与でも臨床症状のコントロールが可能な症例を認めた.3)副作用は評価対象52例中2例に認められ, 2例とも口渇のみであり, 臨床上問題となる重篤なものはなかった.4)有用度は評価時において, "有用"以上67.3%, "やや有用"以上88.5%と高い有用率が得られた, The effects and the safety of oxybutynin hydrochloride were investigated in 52 patients, 17 male and 35 female, with the chief complaints of pollakisuria, urgency and urinary incontinence. Clinical responses to the drug were assessed mainly by the subjective symptoms of the patients. The diagnoses of these patients were neurogenic bladder in 17, unstable bladder in 16 and others in 19 patients. The average administration period was 66.8 days. The rate of global improvement (excellent and good) was 55% in the 2 mg dose given 3 times daily group, 68.2% in the 3 mg dose given 3 times daily group. Side effects, such as dry mouth, were observed in 2 of the 52 patients (3.8%), but no serious side effects were observed. The rate of global utility (remarkable and moderate) was 67.3%. These data indicate that oxybutynin hydrochloride seems to be useful and safe for the treatment of pollakisuria, urgency and urinary incontinence.

The clinical efficacy of oxybutynin hydrochloride was studied on 21 patients with neurogenic bladder or unstable bladder complaining of urinary frequency, urgency and urgent incontinence. Oxybutynin hydrochloride (1 mg/tablet) was administered orally for 26.7 days, on average, 3 mg per day in 3 and 6 mg per day in 18 patients and the usefulness of this drug was assessed subjectively and objectively. Of 21 patients treated, 9 had neurogenic bladder and 10 had unstable bladder. Urinary frequency was normalized in 6 out of 16 (37.5%), urgency ceased in 6 out of 17 (35.7%) and urgent incontinence disappeared in 9 out of 14 (50%) patients. The mean volume at the first desire to void and the maximum cystometric capacity increased significantly on the cystometrogram after the administration of oxybutynin hydrochloride (p less than 0.01). Furthermore, the maximum vesical pressure decreased significantly (p less than 0.05). The maximum urinary flow rate increased slightly (p less than 0.1) and the residual urine volume significantly increased (p less than 0.05) after medication, although no changes were observed in tidal voiding volume or mean urinary flow rate. Of 20 patients, 9 showed improvement globally (45%), although no subjective or objective improvement was observed in 4 (20%) patients. Marked side effects were observed in 5 cases (two of acute urinary retention, each of increased urgency, residual urine and liver dysfunction), and side effects were seen in 10 of the 21 (47.6%) patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PURPOSE This study was carried out to determine the effectiveness of intravesical oxybutynin hydrochloride on urinary urge incontinence in elderly people. METHODS The subjects consisted of 13 patients with an average age of 75 years who demonstrated uninhibited detrusor contraction on cystometrogram. The trial protocol consisted of a pretreatment cystometrogram followed by the intravesical administration of 10 ml solution containing 5 mg oxybutynin hydrochloride (pH 5.85). The urodynamic studies were repeated one hour later. RESULTS The mean bladder capacity before and after one hour of intravesical oxybutynin hydrochloride was 161 +/- 62 ml and 196 +/- 71 ml (mean +/- 1 S.D., n.s.). The rate of improvement was 15.4% (2 cases) in all 13 patients. Four patients out of 13 patients continued intravesical administration of the solution twice daily. Urinary incontinence disappeared in two patients and incontinence was markedly decreased in one. In the remaining patient, urinary incontinence did not change because of increased residual urine. Three patients have continued this therapy over one years and no side effects were observed. In these patients, residual urine volume did not increase. CONCLUSION It is suggested that intravesical oxybutynin hydrochloride is an effective option of therapy for intractable urge incontinence in elderly people, however, the immediate posttreatment cystometrogram was not predictive of the response to intravesical therapy on overactive bladder in the elderly.

The clinical efficacy of oxybutynin hydrochloride was studied on 21 patients with neurogenic bladder or unstable bladder complaining of urinary frequency, urgency and urgent incontinence. Oxybutynin hydrochloride (1 mg/tablet) was administered orally for 26.7 days, on average, 3 mg per day in 3 and 6 mg per day in 18 patients and the usefulness of this drug was assessed subjectively and objectively. Of 21 patients treated, 9 had neurogenic bladder and 10 had unstable bladder. Urinary frequency was normalized in 6 out of 16 (37.5%), urgency ceased in 6 out of 17 (35.7%) and urgent incontinence disappeared in 9 out of 14 (50%) patients. The mean volume at the first desire to void and the maximum cystometric capacity increased significantly on the cystometrogram after the administration of oxybutynin hydrochloride (p less than 0.01). Furthermore, the maximum vesical pressure decreased significantly (p less than 0.05). The maximum urinary flow rate increased slightly (p less than 0.1) and the residual urine volume significantly increased (p less than 0.05) after medication, although no changes were observed in tidal voiding volume or mean urinary flow rate. Of 20 patients, 9 showed improvement globally (45%), although no subjective or objective improvement was observed in 4 (20%) patients. Marked side effects were observed in 5 cases (two of acute urinary retention, each of increased urgency, residual urine and liver dysfunction), and side effects were seen in 10 of the 21 (47.6%) patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects and the safety of oxybutynin hydrochloride were investigated in 52 patients, 17 male and 35 female, with the chief complaints of pollakisuria, urgency and urinary incontinence. Clinical responses to the drug were assessed mainly by the subjective symptoms of the patients. The diagnoses of these patients were neurogenic bladder in 17, unstable bladder in 16 and others in 19 patients. The average administration period was 66.8 days. The rate of global improvement (excellent and good) was 55% in the 2 mg dose given 3 times daily group, 68.2% in the 3 mg dose given 3 times daily group. Side effects, such as dry mouth, were observed in 2 of the 52 patients (3.8%), but no serious side effects were observed. The rate of global utility (remarkable and moderate) was 67.3%. These data indicate that oxybutynin hydrochloride seems to be useful and safe for the treatment of pollakisuria, urgency and urinary incontinence.

In 36 women with cystometric evidence of bladder instability we investigated the efficacy of intravesical instillation of oxybutynin. The intravesical application of oxybutynin had a significant effect regarding the reduction of pollakiuria and nocturia and an improvement of bladder capacity. No local or systemic side effects were noted.

The metabolites, metabolizing organs of oxybutynin and its effect on the induction of drug metabolizing enzymes were investigated in rat, dog and human after oral administrations of oxybutynin and following the results were obtained.1. Eight metabolites of oxybutynin and their glucuronide were identified in the dog and human urine after oral administration.2. About 18 %, and 8.7 to 27.5 % of the administrated dose were excreted as a metabolites to urine in dogs and humans, respectively.3. It was presumed that oxybutynin was metabolized by the following four pathways; a) de-ethylation b) hydrolysis of ester c) hydroxylation at 3' and 4' positions on cyclohexyl ring and d) conjugation of each metabolites.4. The highest metabolic activity for oxybutynin was shown in the rat liver.5. The induction of drug metabolizing enzymes by oxybutynin, administered orally every day for 8 days, was not found.

神経因性膀胱患者10症例に塩酸オキシブチニン1回2 mg 1日3回, 1日量6 mgを投与し, 臨床症状とともに下部尿路機能に及ぼす影響を膀胱内圧測定, 残尿量測定を施行して検討した.1)膀胱内圧測定では本剤投与により初発尿意量は約34%増加し有意差を認めたが, 最大膀胱容量, 最高内圧に関しては明確な変動は認められなかった.残尿量においても, 投与前後における変動は認められなかった.2)自覚症状に対しては頻尿, 尿失禁, 尿意切迫感に対して満足すべき有効率を示した.総合効果においては, 有効以上の有効率で50.0%を得た.3)副作用は10例中4例に認められ, 口渇3例, 下痢1例であった.いずれも一過性, 軽度なもので重篤な副作用は認められなかった, Clinical effects of oxybutynin hydrochloride on lower urinary tract function at a dosage of 2 mg given orally three times daily (6 mg/day), were studied on 10 patients with neurogenic bladder by cystometry and measurement of residual urine. There was a significant increase, of about 34% in FDV, but no significant changes in MBV, or maximum voiding pressure of residual urine after administration. Urinary frequency, incontinence and urgency in subjective symptoms were decreased in patients given this drug. The effective rate (excellent and good) was 50% in global evaluation. Side effects were observed in 4 out of 10 patients; 3 had dry mouth and 1 had diarrhea. There were no serious side effects. These findings suggested that oxybutynin hydrochloride may be a useful drug for neurogenic bladder.

Clinical effects and therapeutic usefulness of oxybutynin hydrochloride were evaluated in a long-term clinical trial on patients with unstable bladders and neurogenic bladders. Of the 46 patients entered into the trial, 37 were those diagnosed with an unstable bladder and 9 with a neurogenic bladder with overactive detrusor. In 37 of the cases (80%), the period of drug administration reached up to 12 weeks and in 16 cases (34%) the drugs were administered for more than 24 weeks. The average administration period was 165.9 days. The average total given dose was 1776.9 mg and average dose per day was 10.7 mg. Excellent and good responses were obtained in 76.3, 88.9 and 69.6% at 12 and 24 weeks after start of administration and at the time of discontinuing the drug, respectively. The cystometric changes at pre- and post-administration were evaluated on 23 cases and revealed a significant increase in volume at first sensation and maximum desire to void. Maximum resting intravesical pressure was significantly declined and uninhibited detrusor contractions were significantly suppressed. Side effects were noted in 11 of the 46 cases (23.9%), most of which were well tolerated by the patients. In 4 cases the drug had to be discontinued because of the side effects. Dry mouth was the most common side effect, occupying almost half of the incidents. No significant abnormality was noted on blood laboratory data, blood pressure or heart rate, following the drug administration. In one case slight increase in serum glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase was encountered, but its relationship with the drug was obscure. The clinical usefulness of this drug (excellent and good) was 78.9, 88.9 and 69.6% at 12 and 24 weeks after start of administration, and at the time of drug discontinuation, respectively. The present long-term trial proved that oxybutynin hydrochloride is an exceedingly effective and safe agent for clinical management of unstable bladder and overactive neurogenic bladder.

The efficacy and safety of long-term administration of oxybutynin hydrochloride in patients with neurogenic bladder and unstable bladder, who complained of urinary frequency, urgency and incontinence, and whose bladder was proved to be uninhibited, reflex, and/or low compliant, were studied at the multi-center hospitals, and the following results were obtained. This study comprised 149 cases but 8 of them were excluded because of the incomplete protocol. Thus, 141 cases (104 neurogenic bladder patients, 33 unstable bladder patients and 4 others) were investigated. The daily dosage of Oxybutynin hydrochloride ranged from 1 to 18 mg, and averaged at 6.6 mg. Since a small daily dosage of 3 mg was administered in 32 cases to examine the minimum effective dosage of the drug, the low average dosage possibly resulted. The clinical optimal dosage seemed to be more than 6.6 mg. The average period of administration in all cases was 161.7 days (1-336 days), and the drug was discontinued in 46 cases (33.6%) on average 62.1 days (1-141 days). The rate of global improvement by this drug estimated at the time of completion was found to be 65.6% with excellent and good and 87.8% with excellent, good and fair. The efficacy of this drug was stable and not decreased during the long-term test period. As to the objective findings studied before, during and after the drug administration, cystometric bladder capacity was significantly increased both first desire to void and the total capacity. Voided volume and residual urine were also increased, but there was no change in the rate of residual urine. Side effects were observed in 37 (26.2%) of 141 cases, and mainly gastrointestinal signs such as dry mouth and constipation. Urological signs such as dysuria and urinary retention were experienced in 8 cases. Regarding the findings of laboratory tests, there were no abnormality except for small changes of some items in normal range. Six children who were younger than 15 years old were subjected to this study. The results of evaluation were similar to those obtained on adults and no side effects were observed. From these findings, oxybutynin hydrochloride is considered an effective and useful drug in patients suffering from neurogenic bladder and unstable bladder with over active bladder condition.

Clinical effects and therapeutic usefulness of oxybutynin hydrochloride were evaluated in a long-term clinical trial on patients with unstable bladders and neurogenic bladders. Of the 46 patients entered into the trial, 37 were those diagnosed with an unstable bladder and 9 with a neurogenic bladder with overactive detrusor. In 37 of the cases (80%), the period of drug administration reached up to 12 weeks and in 16 cases (34%) the drugs were administered for more than 24 weeks. The average administration period was 165.9 days. The average total given dose was 1776.9 mg and average dose per day was 10.7 mg. Excellent and good responses were obtained in 76.3, 88.9 and 69.6% at 12 and 24 weeks after start of administration and at the time of discontinuing the drug, respectively. The cystometric changes at pre- and post-administration were evaluated on 23 cases and revealed a significant increase in volume at first sensation and maximum desire to void. Maximum resting intravesical pressure was significantly declined and uninhibited detrusor contractions were significantly suppressed. Side effects were noted in 11 of the 46 cases (23.9%), most of which were well tolerated by the patients. In 4 cases the drug had to be discontinued because of the side effects. Dry mouth was the most common side effect, occupying almost half of the incidents. No significant abnormality was noted on blood laboratory data, blood pressure or heart rate, following the drug administration. In one case slight increase in serum glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase was encountered, but its relationship with the drug was obscure. The clinical usefulness of this drug (excellent and good) was 78.9, 88.9 and 69.6% at 12 and 24 weeks after start of administration, and at the time of drug discontinuation, respectively. The present long-term trial proved that oxybutynin hydrochloride is an exceedingly effective and safe agent for clinical management of unstable bladder and

Clinical effects of oxybutynin hydrochloride on lower urinary tract function at a dosage of 2 mg given orally three times daily (6 mg/day), were studied on 10 patients with neurogenic bladder by cystometry and measurement of residual urine. There was a significant increase, of about 34% in FDV, but no significant changes in MBV, or maximum voiding pressure of residual urine after administration. Urinary frequency, incontinence and urgency in subjective symptoms were decreased in patients given this drug. The effective rate (excellent and good) was 50% in global evaluation. Side effects were observed in 4 out of 10 patients; 3 had dry mouth and 1 had diarrhea. There were no serious side effects. These findings suggested that oxybutynin hydrochloride may be a useful drug for neurogenic bladder.

The efficacy and safety of long-term administration of oxybutynin hydrochloride in patients with neurogenic bladder and unstable bladder, who complained of urinary frequency, urgency and incontinence, and whose bladder was proved to be uninhibited, reflex, and/or low compliant, were studied at the multi-center hospitals, and the following results were obtained. This study comprised 149 cases but 8 of them were excluded because of the incomplete protocol. Thus, 141 cases (104 neurogenic bladder patients, 33 unstable bladder patients and 4 others) were investigated. The daily dosage of Oxybutynin hydrochloride ranged from 1 to 18 mg, and averaged at 6.6 mg. Since a small daily dosage of 3 mg was administered in 32 cases to examine the minimum effective dosage of the drug, the low average dosage possibly resulted. The clinical optimal dosage seemed to be more than 6.6 mg. The average period of administration in all cases was 161.7 days (1-336 days), and the drug was discontinued in 46 cases (33.6%) on average 62.1 days (1-141 days). The rate of global improvement by this drug estimated at the time of completion was found to be 65.6% with excellent and good and 87.8% with excellent, good and fair. The efficacy of this drug was stable and not decreased during the long-term test period. As to the objective findings studied before, during and after the drug administration, cystometric bladder capacity was significantly increased both first desire to void and the total capacity. Voided volume and residual urine were also increased, but there was no change in the rate of residual urine. Side effects were observed in 37 (26.2%) of 141 cases, and mainly gastrointestinal signs such as dry mouth and constipation. Urological signs such as dysuria and urinary retention were experienced in 8 cases. Regarding the findings of laboratory tests, there were no abnormality except for small changes of some items in normal range. Six children who were younger than 15 years old were subject