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Results for “Administration, Intravesical”

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PubMed1990

[Combined treatment in patients with carcinoma in situ of the urinary bladder using intravesical pirarubicin, irradiation and hyperthermia].

The treatment with hyperthermia in combination with radiation and intravesical pirarubicin (THP-ADM) was preliminary investigated in 5 patients with urinary bladder carcinoma in situ. Following intravesical administration of 30 mg THP-ADM, external irradiation of 3.0 Gy was delivered to the urinary bladder. Immediately then, hyperthermia using Thermotron RF-8 was performed for 50 min (intravesical temperature: 42-43 degrees C for 35 min). After five courses of the treatment, complete response has been maintained for 6, 8, and 9 months in 3 patients. However, in a patient with complete response, urinary cytology became positive in the 6th month after the treatment. In the remaining patient treatment was interrupted after only 3 courses due to urinary irritation, urinary cytology didn't become negative. The side effects of the combined treatment were limited to the transient symptoms of bladder irritation in all patients and thermal burn in 2 patients. These preliminary results suggest that this combined treatment may represent an effective conservative therapy for patients with urinary bladder carcinoma in situ.

Administration, Intravesical↗

PubMed1992

A pilot study comparing different dose levels and administration schedules of interferon-alpha 2b combined with epirubicin for prevention of recurrence in bladder cancer.

A pilot study in 62 patients has been carried out to evaluate the combination of epirubicin and interferon (IFN)-alpha 2b using different doses and schedules of intravesical administration in the prevention of recurrence of bladder cancer. Preliminary results show greater prophylactic efficacy not only when higher doses of epirubicin and IFN-alpha 2b are used but also when a larger interval between instillation of the compounds was used.

Administration, Intravesical↗

PubMed1998

Lidocaine prevents noxious excitation of bladder afferents induced by intravesical capsaicin without interfering with the ensuing sensory desensitization: an experimental study in the rat.

PURPOSE: The effects of the local anesthetic lidocaine on the noxious excitation and subsequent desensitization of bladder sensory fibers, produced by intravesical capsaicin, were evaluated through c-fos activation in the spinal cord. MATERIALS AND METHODS: Noxious excitation was demonstrated by counting Fos-immunoreactive (IR) cells occurring in the rat spinal cord 2 hours after intravesical administration of 1 mM. capsaicin, preceded or not by 2% lidocaine. Desensitization was studied by comparing the number of Fos-IR cells induced by 1% acetic acid in rats treated 24 hours before with 1 mM. intravesical capsaicin preceded or not by 2% lidocaine. RESULTS: Lidocaine instilled previously markedly reduced the number of Fos-IR spinal cells responding to capsaicin-induced bladder afferent excitation. Numbers of Fos-IR cells induced by acetic acid instillation in bladders desensitized by capsaicin administrated 24 hours before were not changed by lidocaine application prior to capsaicin. CONCLUSIONS: These findings suggest that local anesthetic pretreatment of the bladder with lidocaine reduces the capsaicin-induced noxious excitation of the sensory fibers without decreasing their subsequent desensitization.

Administration, Intravesical↗

PubMed2003

[ImmuCyst intravesical (freeze-dried preparation made from the connaught strain of Bacillus Calmette Guérin) for the treatment of superficial bladder cancer and carcinoma in situ of urinary bladder].

UNLABELLED: BCG has been used as a preventive vaccine of tuberculosis worldwide. However, in 1976, Morales et al. reported the effective use against superficial bladder cancer by intravesical administration. In Japan, in July, 1994, Rhone-Poulenc Rorer Japan Inc, started the cooperative clinical studies with Nippon Kayaku Co. Ltd. as an orphan drug. In the phase I/II studies, BCG preparation at 40.5, 81 and 121.5 mg was given intravesically slowly, keeping it for 2 hrs, in the bladder. This was repeated once weekly for 8 weeks. The CR rates were 60, 68.2 and 75% respectively, but there were no significant differences. The major adverse reactions were polyurea, urination pain, urination difficulty, hematurea and urinary leukocytosis which were frequently observed. Beside these, fever, malaise, loss of appetite and GPT elevation were also observed. In the late phase II study, in which 81 mg were given, CR rates in 39 response evaluable cases, was 61.5% (16/26), response rate (CR + PR) was 85.6% (22/26), and CR rate of CIS was 92.6% (12/13). There were responded cases in the recurred cases and those with previous chemotherapy, and the adverse reactions were polyurea, urination pain, urination difficulty, hematurea, malaise and loss of appetite mainly. CONCLUSION: Compared with anticancer drug treatments, BCG prevented the recurrence the disease for a long time. From these studies, freeze-dried BCG preparation (immu-Cyst) seemed to be very useful for the treatment of superficial bladder cancer and carcinoma in situ of urinary bladder.

Adjuvants, Immunologic↗

PubMed1988

Intravesical and intradermal Bacillus Calmette-Guérin application. A phase I study to the toxicity of a Dutch Bacillus Calmette-Guérin preparation in patients with superficial bladder cancer.

In 30 patients toxic side effects of Bacillus Calmette-Guérin (BCG) were evaluated after intradermal and intravesical administration. The BCG preparation (BCG-RIVM) was produced in a homogeneously dispersed culture yielding a relatively high number of culturable particles per milligram dry weight BCG. All patients had a history of recurrent multiple noninvasive superficial transitional cell carcinoma of the bladder, and were previously unsuccessfully treated with intravesical chemotherapy (epodyl and/or adriamycin). BCG-RIVM (1 X 10(9) culturable particles) was instilled in the bladder, in combination with intradermal BCG-RIVM (8 X 10(7) culturable particles) administration once a week for 6 consecutive weeks. BCG was applied intradermally by a multiple-puncture technique. During and after therapy, subjective and objective side effects and toxicity were registered. Hematology and blood chemistry, including hepatic and renal function, was monitored. Only minor toxicity and/or side effects were observed during therapy and for a period of 6 months after treatment. After a period of 7 days no significant amount of BCG bacteria could be detected in the urine of 24 investigated patients.

Administration, Intravesical↗

PubMed1993

Intravesical instillation of oxybutynin hydrochloride for detrusor hyper-reflexia.

The effect of intravesical oxybutynin hydrochloride on detrusor behaviour was studied in 15 patients with urinary incontinence due to detrusor hyper-reflexia by ambulatory bladder monitoring. Twelve patients had a reduction in the frequency and amplitude of hyper-reflexic contractions and incontinence episodes following oxybutynin administration. Intravesical oxybutynin may have a role in the management of patients on intermittent self-catheterisation with detrusor hyper-reflexia who cannot tolerate the side effects of anticholinergic agents, including oxybutynin.

Administration, Intravesical↗

PubMed1990

Phase I and pharmacology study of intravesical mitoxantrone for recurrent superficial bladder tumors.

A phase 1 study of intravesical mitoxantrone was done in patients with superficial bladder tumors recurrent after previous intravesical therapy. Mitoxantrone (5 to 10.5 mg.) was instilled in the bladder via catheter and was left in situ for 2 hours. Each patient received 6 treatments at 1-week intervals. Pharmacology studies were conducted in a subset of consenting patients. Dysuria, urinary frequency and hematuria were dose-limiting at 10 to 10.5 mg., the dose recommended for our phase 2 studies. One patient treated with 7.5 mg. mitoxantrone had bladder contracture after severe bladder injury caused by the drug. The interval free of recurrence increased in 5 of 8 patients treated with 10 to 10.5 mg. mitoxantrone and in 6 of 19 treated at lower dose levels. One patient who had residual evaluable tumor in the bladder at treatment experienced a complete remission for 16 months. Only 1 of 18 patients who underwent pharmacology studies had any mitoxantrone detectable in the blood after intravesical administration. This patient had severe irritative symptoms at treatment. No systemic toxicity was noted in any patient. Of the mitoxantrone instilled into the bladder 33 to 100% (mean 75%) was recovered in the specimen voided at the end of treatment. In summary, intravesical mitoxantrone is reasonably well tolerated and should be studied further at a dose of 10 mg. per week for 6 weeks. Caution should be exercised, since bladder contracture was seen in 1 patient. Systemic absorption and toxicity are negligible.

Administration, Intravesical↗

PubMed2006

Kinetic model of drug distribution in the urinary bladder wall following intravesical instillation.

Intravesical administration of cytotoxic agents is commonly used in urological practice for treatment of superficial bladder cancer. The leading motive is optimisation of drug delivery near the site of action and reduction of systemic toxicity. Bladder pharmacokinetics is complicated by several mechanisms. The objectives of this work were to develop a kinetic model of drug distribution in the bladder wall following intravesical instillation and to study the effect of various parameters on tissue and systemic drug exposure and explore the potential benefits of permeability enhancing effects of chitosan (CH) and polycarbophil (PC) through simulation. Key elements of the model are variable urinary drug concentration due to urine formation and voiding, biphasic diffusion in the bladder tissue and systemic absorption. Model parameters were estimated from bladder-tissue concentration profiles obtained in previous in vitro experiments with pipemidic acid (PPA) as a model drug. The results support further investigations on application of CH and PC in intravesical drug delivery. Both polymers increase permeability of the bladder wall by diffusion enhancement in the urothelium and presumably by improving the contact with the bladder surface. The developed mathematical model could serve for optimisation of intravesical drug delivery and future development of intravesical drug delivery systems.

Acrylic Resins↗

PubMed2000

Cystoscopic diagnosis of bladder cancer by intravesical instillation of 5-aminolevulinic acid induced porphyrin fluorescence--the Singapore experience.

OBJECTIVES: 1) To determine whether fluorescence cystoscopy after intravesical administration of 5-aminolevulinic acid (5-ALA) is more sensitive in detection of dysplasia and bladder cancer when compared with conventional cystoscopy. 2) To determine the safety of using 5-ALA. MATERIALS AND METHODS: A 3% 5-ALA solution was instilled intravesically before cystoscopy in 41 patients. The 5-ALA-induced porphyrin fluorescence was excited by violet light from a xenon arc lamp (lambda 375-440 mm). RESULTS: Among the 175 biopsies obtained, the sensitivity of the fluorescence cystoscopy was greater than that of conventional cystoscopy (89.1% versus 65.6%, P < 0.05). Specificity was at 64.8% and 83.8% respectively with P < 0.05. Duration of ALA instillation did not seem to affect the sensitivity and specificity of photodynamic diagnosis. The procedures were well tolerated by all patients with no additional complication. CONCLUSIONS: Fluorescence-guided biopsies are more sensitive than random biopsies in detecting dysplasia or bladder cancer without additional risk or complication. The duration of ALA instillation did not seem to affect the accuracy of photodynamic diagnosis.

Administration, Intravesical↗

PubMed2002

Intravesical sodium hyaluronate inhibits the rat urinary mast cell mediator increase triggered by acute immobilization stress.

PURPOSE: Mast cell activation and stress have been suggested as factors in the pathogenesis of interstitial cystitis, a painful disorder of the bladder that is diagnosed more frequently in women and characterized by increased urgency and frequency with absent infection. Intravesical sodium hyaluronate has been used to treat interstitial cystitis due to its possible replenishment of bladder glycosaminoglycans. We investigated the effect of sodium hyaluronate on the activation of bladder mast cell and release of proinflammatory mediators in the urine induced by acute immobilization stress in rats. MATERIALS AND METHODS: Using anesthesia a catheter was inserted in the bladder of 170 gm. female Sprague-Dawley rats. After emptying post-void residual urine a solution of normal saline, 0.08% or 0.4% sodium hyaluronate was introduced for 30 minutes. Each rat was allowed to recover from anesthesia and stressed for 30 minutes by confining it in a clear acrylic plastic immobilizer, while urine was continuously collected. Urinary histamine, rat mast cell protease-I and interleukin (IL)-6 were then determined. At the end of the experiments each rat was sacrificed by CO2 asphyxiation, and the bladder was removed and fixed with 4% paraformaldehyde. Frozen sections were stained with acidified toluidine blue, and the mast cell number and degree of activation were determined by granule extrusion and reduced cellular staining. RESULTS: Mean bladder mast cell activation plus or minus standard deviation in 6 control rats was 30.4% +/- 3.7% but it increased to 76.2% +/- 6.1% in 6 stressed animals (p = 0.0001). Intravesical administration of 0.4% sodium hyaluronate for 30 minutes in 6 rats before stress reduced mean bladder mast cell activation by 69.7% to 23.1% +/- 6.1% compared with stressed controls (p = 0.0003). However, compared to itself before stress there was no significant difference, indicating complete inhibition in 6 rats. Intravesical 0.08% sodium hyaluronate had a weaker inhibitory effect in 6 rats, decreasing mean degranulation by 22.5% to 59.1% +/- 7.6% (p = 0.02). In 6 rats stress increased the total mean amount of urinary rat mast cell protease-I by 271% from 0.14 +/- 0.09 to 0.52 +/- 0.17 ng. (p = 0.008). Pretreatment with 0.4% sodium hyaluronate reduced mean rat mast cell protease-I 80.8% compared with stressed controls (p = 0.008) and prevented any increase in response to stress in the same group of 8 rats with a mean pre-stress and post-stress level of 0.09 +/- 0.04 and 0.1 +/- 0.04 ng., respectively (p = 0.8). Acute stress increased mean urinary histamine in 6 rats 40.2% from 137.3 +/- 29.7 before to 193.7 +/- 7.6 ng./ml. after stress (p = 0.004). Pretreatment with 0.4% sodium hyaluronate reduced mean histamine 7.1% compared with stressed controls but completely prevented any increase in the same group of 8 rats, in which it was 174.5 +/- 23.1 before and remained 179.4 +/- 9.9 ng./ml. after stress (p = 0.75). Acute stress in 7 rats also increased the mean amount of IL-6 released in the urine by 31.5% from 775.9 +/- 69.2 to 1,021.1 +/- 93.3 pg./ml. (p = 0.007). Pretreatment with 0.4% sodium hyaluronate in 9 rats reduced mean IL-6 17% compared with stressed controls but again prevented any increase from baseline, since the value was 898.6 +/- 299.3 before and 824.4 +/- 196.4 pg./ml. after stress (p = 0.03). CONCLUSIONS: Immobilization stress induces bladder mast cell activation and the secretion of proinflammatory mediators, which are inhibited by sodium hyaluronate. Intravesical sodium hyaluronate may be a useful therapeutic option for interstitial cystitis, especially in patients with bladder mastocytosis who have symptom exacerbation with stress.

Administration, Intravesical↗

PubMedDate not supplied

Intravesical gemcitabine in superficial bladder cancer: a phase II safety, efficacy and pharmacokinetic study.

BACKGROUND: We investigated the safety, efficacy and pharmacokinetics of the intravesical administration of 2000 mg gemcitabine once a week in the four weeks before transurethral resection of superficial bladder cancer (TUR), and in the four successive weeks. MATERIALS AND METHODS: Nine patients with superficial transitional cell bladder carcinoma were studied. Two thousand mg of gemcitabine dissolved in 50 ml of distilled water were administered intravesically. The dwell time was 60 min. The pharmacokinetics of gemcitabine and its metabolite, 2',2'-difluorodeoxyuridine (dFdU), were studied in plasma and urine before and after TUR. Cystoscopy was repeated 30 days after completion of the TUR treatment and subsequently at time intervals of one or two months. RESULTS: No systemic toxicity was noted, and only three patients displayed modest signs of local toxicity. One patient had recurrence 1 month after TUR, three between 3 and 6 months, and another three after 8, 11 and 18 months, respectively; two were recurrence-free after 21 and 22 months, respectively. The peak plasma concentrations of gemcitabine never exceeded 1000 ng/ml before TUR and 350 ng/ml after TUR, and declined rapidly. The plasma levels of dFdU were higher than those of gemcitabine, increased until 60 min and then declined little. Between 52% and 100% of the gemcitabine dose was present in voided urine. CONCLUSION: Intravesical gemcitabine, at the dose of 2000 mg, is well tolerated, is associated with minimal systemic absorption and has a moderate efficacy in the treatment of superficial bladder cancer.

Administration, Intravesical↗

PubMed2003

Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer.

BACKGROUND: Tumour recurrence following transurethral resection (TUR) for Ta and T1 bladder cancer is a major clinical problem. Intravesical administration of mitomycin C (MMC) or bacillus Calmette-Guerin (BCG) has proven prophylactic activity but both are associated with local and systemic side-effects. A systematic review was carried out to compare the efficacy of these two agents. OBJECTIVES: To undertake a systematic review and meta-analysis comparing intravesical mitomycin C and Bacillus Calmette-Guerin in terms of tumour recurrence, disease progression and overall survival in Ta and T1 bladder cancer. Treatment-related toxicities would also be evaluated. SEARCH STRATEGY: A comprehensive search of MEDLINE, EMBASE, Healthstar, Cochrane Controlled Trials Register, Cancerlit, and DARE was performed, and hand searching of relevant journals undertaken. SELECTION CRITERIA: Trials in any language were included in the meta-analysis if they were properly randomised, included medium to high risk patients with Ta or T1 bladder cancer and compared intravesical MMC versus BCG. DATA COLLECTION AND ANALYSIS: Trial eligibility, methodological quality and data extraction were assessed independently by two reviewers. Time to event analysis was evaluated using log hazard ratios, with a sensitivity analysis for subgroups according to patient's risk of recurrence. MAIN RESULTS: Twenty-five articles were identified but only seven were considered eligible. This represented 1901 evaluable patients in total, 820 randomised to MMC and 1081 to BCG. Six trials had sufficient data for meta-analysis and included 1527 patients, 693 in the mitomycin arm and 834 in the BCG arm. The weighted mean log hazard ratio (variance) for tumour recurrence for the six trials was - 0.022 (0.005). This indicated no significant difference between MMC and BCG (p = 0.76). However, the meta-analysis indicated evidence of significant heterogeneity between trials (p = 0.001). A subgroup analysis of three trials that included only high risk Ta and T1 patients indicated no heterogeneity (p = 0.25) and a log hazard ratio (variance) for recurrence of -0.371 ( 0.012). With MMC used as the control in the meta-analysis, a negative ratio is in favour of BCG and, in this case, is highly significant (p = 0.0008). The seventh trial, in abstract form only, used BCG in low doses for two arms of the trial (27 mg and 13.5mg) compared to a standard dose of mitomycin C (30mg), and reported a significantly reduced recurrent rate with BCG (27mg) compared to mitomycin C (p = 0.001). Only two trials included sufficient data to analyse disease progression and survival, representing a total of 681 patients; 338 randomised to BCG and 343 to MMC. There was no significant difference between MMC and BCG for disease progression (log hazard ratio + variance: 0.044 + 0.04, p = 0.16) or survival (-0.112 + 0.03, p = 0.50). Local toxicities (dysuria, cystitis, frequency, and haematuria) were associated with both MMC (30%) and BCG (44%). Systemic toxicities, such as chills, fever and malaise, were observed with both MMC and BCG (12% and 19%, respectively) although skin rash was more common with MMC. REVIEWER'S CONCLUSIONS: The data from the present meta-analysis indicate that tumour recurrence was significantly reduced with intravesical BCG compared to MMC only in the subgroup of patients at high risk of tumour recurrence. However, there was no difference in terms of disease progression or survival, and the decision to use either agent might be based on adverse events and cost.

Administration, Intravesical↗

PubMed1995

Treatment of neurogenic bladder dysfunction in infants and children with neurospinal dysraphism with clean intermittent (self)catheterisation and optimized intravesical oxybutynin hydrochloride therapy.

Clean intermittent (self)catheterisation (CIC) in combination with oral anticholinergic drugs (oxybutynin hydrochloride [OH] is the present standard therapy for neurogenic bladder dysfunction (NBD) with detrusor hyperactivity. However, complete suppression of detrusor contractions and complete urinary continence is not always obtained despite maximal dosage, and the high incidence of severe systemic anticholinergic side-effects often impairs therapeutic compliance, resulting in dose reduction or even discontinuation of therapy. The intravesical administration of OH has been shown recently to be an effective alternative for treating persistent detrusor hyperactivity, and occurrence and severity of systemic side-effects appeared to be significantly decreased. However, available data are limited from a paediatric view. Furthermore, it is our belief that the use of crushed OH tablets with consequent problems of impracticability accounts for the variable long-term patient compliance reported to be the only disadvantage to intravesical OH. Using an optimized drug preparation we demonstrate the superiority of intravesical OH for treatment of NBD in 15 children (range 0.6-13.75 years, mean 6.1) with incomplete detrusor activity suppression and/or intolerable systemic side-effects on oral OH therapy. Since the previous reported problems of impracticability and variable long-term patient compliance can be resolved by optimized drug preparation, we therefore conclude that the era of crushing OH tablets should be over in order to allow the intravesical OH therapy on a long-lasting and large-scale basis.

Administration, Intravesical↗

PubMed2004

New therapeutic options for refractory neurogenic detrusor overactivity.

AIM: Current pharmacologic treatment of detrusor overactivity relies on anticholinergic drugs. However, they often have untolerable side effects so that they are administered in doses insufficient to restore urinary continence. Recently, intravesical instillations and injections into the detrusor muscle of new pharmacological agents have been developed. The present study report our own experience in the treatment of detrusor overactivity with intravesical administrations of vanilloid agents and with botulinum-A toxin injections into the detrusor muscle in a group of spinal cord injured patients. In particular, we compared the clinical and urodynamic effects of the 2 drugs in an attempt to find a new and valid therapeutic option in those cases unresponsive to conventional treatment. METHODS: Seventy-five patients with spinal cord injury and refractory detrusor overactivity were included in the study: 35 patients received repeated intravesical instillations of resiniferatoxin (RTX) dissolved in normal saline; 40 patients received repeated injections of 300 units botulinum A-toxin diluted in 30 ml normal saline. Clinical assessment and urodynamics were performed at baseline and 6, 12 and 24 months after treatment. RESULTS: With both treatments there was a significant reduction in mean catheterization and episodes of incontinence and a significant increase in mean first involuntary detrusor contraction and in mean maximum bladder capacity at 6, 12 and 24 months after therapy. We did not detect any local side effects with either treatment. Botulinum-A toxin significantly reduced also the maximum pressure of uninhibited detrusor contractions more than RTX at all follow-up time points. CONCLUSION: In patients with spinal cord injury and refractory detrusor overactivity intravesical RTX and botulinum-A toxin injections into the detrusor muscle provided beneficial clinical and urodynamic results with reduction of detrusor overactivity and restoration of urinary continence in most patients. Botulinum-A toxin injection provided better clinical and urodynamic benefits than intravesical RTX.

Administration, Intravesical↗

PubMed2000

An improved intravesical model using human bladder cancer cell lines to optimize gene and other therapies.

Orthotopic implantation of human bladder cancer cells into immunodeficient mice is an important tool for studying the biology and effects of therapy. Nevertheless, the incidence of tumor implantation and growth by transurethral instillation of the human bladder cancer cells into murine bladders has been low or not reproducible. However, using a modified intravesical technique and the human bladder cancer cell lines, KU-7 and UM-UC-2, we have been able to obtain a high and reproducible incidence of superficial bladder tumors. Furthermore, intravesical administration of the LacZ adenovirus vector resulted in significant beta-galactosidase expression in these bladder tumors as well as the normal urothelium, which was associated with the removal of the glycosoaminoglycan layer. Because this modified technique produces a high incidence of superficial human tumor growth and allows the efficacy of gene transfer to be evaluated, it should be a useful model for the study of intravesical gene therapy for human bladder cancer.

Adenoviridae↗

PubMed1991

In vitro intravesical instillation of anticholinergic, antispasmodic and calcium blocking agents to decrease bladder contractility.

We investigated the effect of intravesical administration of atropine, oxybutynin, verapamil, diltiazem, and imipramine on pressure responses of the rabbit in vitro whole bladder model. All drugs investigated suppressed the pressure responses to field stimulation and bethanechol in a time-dependent manner (maximum inhibition at 90-120 min). Atropine and oxybutynin suppressed the contractile response to bethanechol to a much greater extent than that to field stimulation. These results suggest that the use of self-intravesical instillation might be a good therapeutic approach for patients with detrusor hyperreflexia, especially those who are already managed by intermittent catheterization.

Administration, Intravesical↗

PubMed1993

Bladder damage in mice after single and repeated intravesical instillations of mitomycin C or doxorubicin.

Functional and histological damage after intravesical administration of mitomycin C or doxorubicin were studied in mouse bladders. Dosing schedules were based on those commonly used in the clinic, and bladder function was assessed from changes in urination frequency. Repeated weekly instillations of 1 mg./ml. mitomycin C induced a transient three-fold increase in Frequency Index (FI) with recovery to control levels within 3 weeks. Weekly instillations of 6 mg./ml. doxorubicin also resulted in a three-fold increase in FI, but lower doses produced only minimal changes. There was, again, full recovery within 3 weeks. Our experiments indicate that repeated intravesical instillations of mitomycin C or doxorubicin are well tolerated, with rapid recovery from functional damage within a few weeks of cessation of therapy. There was significantly less damage after repeated instillations of clinically relevant doses of doxorubicin than mitomycin C.

Administration, Intravesical↗

PubMed2001

Analysis of the afferent limb of the vesicovascular reflex using neurotoxins, resiniferatoxin and capsaicin.

The afferent limb of the vesicovascular reflex (VV-R) evoked by distension or contraction of the urinary bladder (UB) was studied in urethane-anesthetized female rats by examining the changes in VV-R after administration of C-fiber afferent neurotoxins [capsaicin and resiniferatoxin (RTX)]. Systemic arterial blood pressure increased parallel (5.1 to 53.7 mmHg) with graded increases in UB pressure (20 to 80 cm H(2)O) or during UB contractions. The arterial pressor response to UB distension was significantly reduced (60-85%) by acute or chronic (4 days earlier) intravesical administration of RTX (100-1,000 nM) or by capsaicin (125 mg/kg sc) pretreatment (4 days earlier). Chronic neurotoxin treatments also increased the volume threshold (>100%) for eliciting micturition in anesthetized rats but did not change voiding pressure. Acute RTX treatment (10-50 nM) did not alter the arterial pressor response during reflex UB contractions, whereas higher concentrations of RTX (100-1,000 nM) blocked reflex bladder contractions. It is concluded that VV-R is triggered primarily by distension- and contraction-sensitive C-fiber afferents located, respectively, near the luminal surface and deeper in the muscle layers of the bladder.

Administration, Intravesical↗