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BACKGROUND: Dementia is a brain disorder characterized by the permanent loss of higher cognitive functions. A number of vasodilatory drug treatments are prescribed for dementia. Naftidrofuryl is one such medicine which is reported to improve clinical symptoms significantly. The efficacy and possible adverse events of naftidrofuryl need to be reviewed systematically and assessed critically to inform clinical practice and guide the continued search for new treatment regimens. OBJECTIVES: To evaluate the efficacy and safety of naftidrofuryl in the treatment of dementia. SEARCH METHODS: We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 11 January 2011 using the terms: naftidrofuryl. ALOIS contains records of clinical trials from major healthcare databases (MEDLINE, EMBASE, PsycINFO, LILACS and CINAHL), trial registries (such as ClinicalTrials.gov) and grey literature sources. SELECTION CRITERIA: Randomised placebo-controlled trials in which patients with dementia were treated with naftidrofuryl were considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data using data extraction forms. The domains assessed for risk of bias were sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting. We used odds ratios (OR) for reporting dichotomous data, and mean differences (MD) and standardized mean differences (SMD) for continuous data. We assessed statistical heterogeneity using the I(2) statistic. MAIN RESULTS: We identified nine randomised controlled trials involving 847 patients with Alzheimer's disease, vascular dementia, mixed dementia, senile dementia and unspecified dementia. The beneficial effects were found on functional performance and behaviour (-1.04 standardized points, 95% CI -1.73 to -0.35, P = 0.003) with a high-level heterogeneity (I(2) = 54%), and mood (-0.80 standardized points, 95% CI -1.26 to -0.34, P=0.0006) for patients with dementia, as well as on cognitive function (-0.36 standardized points, 95% CI -0.71 to -0.02, P=0.04). However, this was not confirmed by clinical global measures. Naftidrofuryl was found to be well-tolerated by patients with dementia. AUTHORS' CONCLUSIONS: Oral administration of naftidrofuryl is well-tolerated by patients with dementia.The low-quality evidence shows that, by use of naftidrofuryl, people with dementia may benefit on performance, behaviour, cognition, and mood. However, the benefit on global impression is inconsistent and unconvincing.

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Naftidrofuryl (Praxilene) is a vasodilator that has been used in the treatment of intermittent claudication for >30 years in Europe to improve walking distance and provide symptomatic relief. However, earlier trials had inconsistencies in design and the clinical relevance of the treatment effect has been controversial. Recent randomised, double-blind, placebo-controlled trials, however, have generally been conducted in accordance with updated methodology guidelines. In these studies, naftidrofuryl 200mg three times daily improved pain-free and maximal walking distances and health-related quality of life by a significantly greater extent than placebo in patients with intermittent claudication. The magnitude of these effects appears to support claims that the effects of naftidrofuryl are clinically relevant in these patients.

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Naftidrofuryl (CAS 31329-57-4) is used, mainly in elderly patients, in the treatment of various vascular disorders. The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in caucasian male and female subjects with renal impairment versus healthy volunteers. This prospective and open study was conducted in three parallel groups: Group A = healthy subjects with a Cl(CR) > 80 ml/min, Group B = uraemic patients with a 20 < or = Cl(CR) < 40 ml/min, Group C = uraemic patients with a Cl(CR) < 20 ml/min. Blood samples were taken over a period of 32 h after dosing. The mean values (+/-SD) of the pharmacokinetic parameters of naftidrofuryl for group A were as follows: tmax: 1.3 h (median), Cmax: 174 +/- 46 ng/ml, t(1/2 beta): 4.4 +/- 1.1 h, AUC(0-infinity): 1541 +/- 384 ng x h/ml; for group B: tmax: 2.5 h (median), Cmax: 239 +/- 94 ng/ml, t(1/2 beta): 5.0 +/- 1.2 h, AUC(0-infinity): 2361 +/- 751 ng x h/ml; for group C: tmax: 3.0 h (median), Cmax: 236 +/- 104 ng/ml, t(1/2 beta): 5.0 +/- 2.1 h, AUC(0-infinity): 2488 +/- 2003 ng x h/ml. The statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each group. No significant difference between each group was observed. In conclusion, renal insufficiency did not appear to influence the pharmacokinetic profile of oral naftidrofuryl.

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BACKGROUND: We report in this paper the findings of a pooled analysis of 3 previously published studies undertaken in Germany, France and Belgium to assess the effects of naftidrofuryl on the quality of life of patients with intermittent claudication. METHODS: A total of 754 patients were randomised in the 3 studies, 709 of whom (358 naftidrofuryl, 351 placebo) were available for the primary intention-to-treat analysis. The primary outcome variable was the change in the disease-related limitation of the quality of life as measured by the CLAU-S questionnaire. This instrument which has been validated in an international study, comprises 47 questions covering 5 dimensions: "daily living", "pain", "social life", "disease specific anxiety" and "mood". RESULTS: A multivariate analysis of covariance adjusted for baseline values, study effect and first order study treatment interaction, demonstrated the global superiority of naftidrofuryl over placebo (p<0.001). A separate covariance analysis for the 5 dimensions showed highly significant differences for "daily living", "pain", "social life" and "mood" (all p<0.01). CONCLUSIONS: In conclusion, this pooled analysis has shown that naftidrofuryl can significantly improve the quality of life of patients with intermittent claudication. These findings, taken together with evidence from previous studies that it improves treadmill walking distances, suggest that naftidrofuryl can play a useful role in the treatment of this condition.

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BACKGROUND: The efficacy and safety of naftidrofuryl were assessed in a double blind, placebo controlled, parallel group study, in patients presenting with intermittent claudication, according to the latest European guidelines. METHODS: The outpatients selected were of both sexes, aged 35 to 85, with moderately severe chronic, stable intermittent claudication and a pain-free (PFWD) and maximum walking distance (MWD) on the treadmill of between 100 and 300 metres. They received naftidrofuryl 200 mg tid or placebo for six months and were then assessed during a six-month follow-up period without treatment. The primary outcome measures were the pain-free walking distance and maximum walking distance. RESULTS: Of the 221 selected patients, 196 were randomised and 181 entered the intention-to-treat analysis. The two groups were well matched for demographic variables, risk factors and history of vascular disease. After six months of treatment, patients who received naftidrofuryl had a 92% im-provement of geometric pain-free walking distance versus 17% in the placebo group (p < 0.001) and an 83% improvement of geometric maximum walking distance versus 14% in the placebo group (p < 0.001). During the follow-up period without treatment, the walking distances of the patients in the naftidrofuryl group significantly decreased. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This study demonstrated the efficacy of naftidrofuryl versus placebo in patients with intermittent claudication with a highly significant and clinically relevant difference and confirmed its good safety profile.

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The design of this study was based on the European guidelines for the treatment of Alzheimer's disease. After a placebo run-in period of 4 weeks, patients with a diagnosis of vascular dementia (VaD) were randomised to receive either 400 mg naftidrofuryl/day, 600 mg naftidrofuryl/day or placebo for 6 months. The patients were assessed using the ADAS-cog, the SCAG, the NOSGER and the CGI item 2 scale. The primary analysis was undertaken on the ITT population. At the end of the study, significantly more patients in the treatment groups showed no deterioration on both ADAS-cog and SCAG scales compared with placebo (400 mg p = 0.005, 600mg p = 0.015). There were also significant differences between the active and placebo groups for the individual scales. This study has demonstrated that treatment with naftidrofuryl can slow the rate of deterioration of patients with vascular dementia.

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BACKGROUND: Dementia is a cerebral disorder resulting in a progressive deterioration of intellectual function that compromises the patient's ability to function. The diagnostic criteria for dementia are primarily clinical and are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Hachinski score and computed tomography of the brain help distinguish between degenerative and vascular dementias. OBJECTIVE: This study examined the efficacy of naftidrofuryl in patients with vascular or mixed dementia. METHODS: This multicenter, randomized, double-blind study compared naftidrofuryl 600 mg/d with placebo for 1 year in patients with vascular or mixed dementia. A preliminary 2-month washout period allowed selection of patients who were compliant with treatment. The end point was change in the scores on the Alzheimer Disease Assessment Scale cognitive subscale and the Mini-Mental State Examination. RESULTS: Eighty-four patients were assessable on an intent-to-treat basis, and 74 were assessable for the per-protocol analysis (on-treatment). Statistically significant improvements in cognitive and global function were observed in patients receiving naftidrofuryl. Naftidrofuryl was well tolerated, and produced no clinically significant abnormalities in laboratory test results. CONCLUSION: The results of this study suggest that naftidrofuryl is effective and well tolerated in treating the symptoms of vascular and mixed dementia.

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BACKGROUND: Using a disease specific questionnaire, the CLAU-S, we undertook a double blind, placebo controlled study in patients with intermittent claudication to determine whether the increase in the pain-free walking distance, previously demonstrated with naftidrofuryl, is reflected as an improvement in the patients' quality of life. PATIENTS AND METHODS: 287 patients, with stable intermittent claudication for at least 3 months were entered into the study. Following an initial one month placebo run-in, patients were randomised to either naftidrofuryl, at a dosage of 200 mg three times daily, or matching placebo, for 6 months. All patients completed the self-administered CLAU-S questionnaire which is divided into 6 dimensions, before the start of treatment, at 3 and 6 months. Statistical analysis was undertaken on an intention-to-treat (ITT) basis which included all patients know to have taken at least one dose of the drug and to have provided key data on at least one occasion after baseline. For each of the CLAU-S dimensions the two groups were compared with respect to difference between the initial and final values. RESULTS: 255 patients (133 naftidrofuryl, 122 placebo) were eligible for the ITT analysis. Significant improvements, in favour of the active medication, were seen for the dimensions "daily living", "pain", "disease specific anxiety" and "mood". A multivariate analysis of covariance, which took into account such factors as initial score, age and sex confirmed the global superiority of naftidrofuryl (p = 0.004). CONCLUSIONS: In this placebo controlled study, using a disease specific questionnaire, naftidrofuryl has been shown to significantly improve several aspects of the quality of life of patients with intermittent claudication.

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PURPOSE: To evaluate the effects of an S2 specific antiserotonine agent (Naftidrofuryl) on the optic nerve head blood flow in glaucomatous patient. PATIENTS AND METHOD: 11 glaucomatous subjects were enrolled in the study. After administration of 200 mg naftidrofuryl twice daily for 7 days: values of optic nerve head blood flow (Fonh), velocity and volume were recorded in the temporal rim and cup of the optic nerve head. Blood flow measurements were performed by laser doppler flow-metry at day 0 and day 7 before and one and two hours after drug administration. RESULTS: Our study showed a significant improvement of perfusion pressure (p = 0.02) at day 7 and an increase of mean ophthalmique artery pressure (p = 0.03). DISCUSSION: Our preliminary results on a small number of patients and a short follow-up indicate that the use of naftidrofuryl may enhance optic nerve head blood flow in glaucomatous patients. Further studies may confirm these results.

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The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl (CAS 3200-06-4) after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in Caucasian male and female elderly healthy volunteers versus young healthy volunteers. Thirty healthy volunteers were included in a randomised phase I trial in 3 parallel groups of 10 subjects aged 18-35 years (group 1), 60-70 years (group 2) and 70-80 years (group 3). Blood samples were taken over a period of 24 h after dosing for evaluation of the pharmacokinetics of naftidrofuryl. The Cmax, tmax, AUC0-t parameters were measured and t1/2 and AUC0-alpha were calculated by a model independent method. The mean (+/- SD) pharmacokinetic parameters of naftidrofuryl after single oral administration of 200 mg of naftidrofuryl for group 1 were as follows: tmax 3.5 h (median), Cmax 284 +/- 136 ng/ml, t1/2 3.69 +/- 1.30 h, AUC0-t 1865 +/- 905 h.ng/ml and AUC0-inf 2055 +/- 901 h.ng/ml; for group 2: tmax 2.75 h (median), Cmax 282 +/- 165 ng/ml, t1/2 3.03 +/- 1.08 h, AUC0-t 1783 +/- 1147 h.ng/ml and AUC0-inf 1856 +/- 1158 h.ng/ml; for group 3: tmax 2.5 h (median), Cmax 271 +/- 86 ng/ml, t1/2 3.50 +/- 1.29 h, AUC0-t 1742 +/- 544 h.ng/ml and AUC0-inf 1834 +/- 549 h.ng/ml. Statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each age group. The results of the pharmacokinetic and statistical analysis showed no significant difference between each age group. The mean pharmacokinetic parameters of naftidrofuryl after single oral administration of 200 mg of naftidrofuryl in the whole population were as follows: tmax 2.75 h (median), for Cmax 279 +/- 128 ng/ml, t1/2 3.41 +/- 1.22 h, AUC0-t 1797 +/- 870 h.ng/ml for AUC0-inf 1910 +/- 877 h.ng/ml. In conclusion, advanced age did not appear to influence the pharmacokinetic profile of oral naftidrofuryl, and therefore it is not necessary to adjust the dosage of naftidrofuryl in this population.

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Crystalluria is important in the evaluation of patients with urinary stone and is more frequently encountered in elderly than in younger adults. After noting that calcium oxalate monohydrate crystalluria was higher in elderly patients, we undertook a study to determine if oral treatment with naftidrofuryl oxalate, a drug frequently prescribed for elderly patients in France, was associated with crystalluria. The presence of early morning crystalluria was assessed in non-stone-forming patients hospitalized in a geriatric department. We studied 251 patients without a history of nephrolithiasis (mean age; 81.6 +/- 8.5 years) of whom 49 had been treated orally with naftidrofuryl oxalate at a mean dosage of 485 +/- 120 mg/24h. We identified and quantified the crystals in one early morning urine sample kept at room temperature. The frequency of crystalluria in elderly patients without stones who were not taking naftidrofuryl oxalate was 31.7% compared with only 6% in the general adult population. In this group, mainly calcium phosphate crystals were found. In patients who received naftidrofuryl oxalate, the frequency of crystalluria was 51% of which the major component was calcium oxalate monohydrate and not calcium phosphate. Naftidrofuryl oxalate may enhance crystal formation in elderly patients. This should be taken into account, particularly when other predisposing factors for nephrolithiasis are present, and a preventive increase in fluid intake considered.

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We report two cases of acute renal failure in patients with arteriosclerosis obliterans treated by intravenous infusion of naftidrofuryl oxalate. At renal biopsy the histological lesions were identical with those found in ARF due to hyperoxaluria of other causes, revealing tubular epithelial necrosis and massive intratubular precipitation of calcium oxalate monohydrate (C1) crystals. A second study was then conducted in four other patients with arteriosclerosis obliterans to evaluate serum and urinary levels of oxalate, and crystalluria during the intravenous administration of 800 mg of naftidrofuryl oxalate per day for 10 days. During the course of treatment, the serum and urinary oxalate levels were found to increase substantially, with the gradual onset of massive C1 crystalluria. These results indicate that naftidrofuryl oxalate was responsible for the acute renal failure in the first two patients. High intravenous doses of naftidrofuryl oxalate must be used cautiously, with close surveillance of renal function.

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80 patients with idiopathic sudden hearing loss existing no longer than 10 days were included in a randomised reference-controlled study. The therapeutic value of Ginkgo EGb 761 (Tebonin) + HAES was compared to that of Naftidrofuryl (Dusodril)+HAES. The main mechanisms of action of EGb 761 are a vasoregulating activity (increased blood flow), the platelet activating factor antagonism and a prevention of membrane damage caused by free radicals. Naftidrofuryl has antiserotonergic and therefore vasodilatory properties. The statistical analysis of the audiometric data was performed in measuring the relative hearing gain as described by Eibach 1979. After one week of observation, 40% of the patients in each group showed a complete remission of hearing loss. This was also observed by other authors who had compared other drugs. Therefore, in these cases, it is most likely that spontaneous recovery is the most important factor. After two and three weeks of observation, measuring the relative hearing gain, there was a significant borderline benefit of EGb 761 (p = 0.06) without any side effects. Some patients of the reference group developed side effects such as orthostatic dysregulation or headache or sleep disturbances. Minimising side effects should be one of the most important goals in therapy of sudden hearing loss until the efficiency of infusion therapy is proved.

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The case of a 7-year-old boy who suffered a convulsion during parenteral infusion of naftidrofuryl is reported. The effectiveness of adding naftidrofuryl to infusions designed to increase cochlear blood flow in cases of sudden hearing loss has been keenly debated in the otologic literature. Several hazards are associated with this drug, especially when the infusion is performed too fast. We recommend an individual decision for each patient suffering from cochleo-vestibular disorder based on the neurological and cardiological risk factors and the therapeutic possibilities.

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