Treatment Of Chronic Gout Research Articles

Development and characterization of liposomal formulations containing sesquiterpene lactones for the treatment of chronic gout

Gout and hyperuricemia are characterized by high uric acid levels, and their treatment involves medications that have adverse effects. In this study, we evaluated oral liposomal formulations with eremantholide C and goyazensolide as a novel approach to reduce the toxicity associated with these substances while maintaining their anti-hyperuricemic activity. We characterized the formulations and evaluated them based on encapsulation efficiency and stability over 12 months and under simulated physiological environments. We determined the toxicity of the liposomal formulations in Caco-2 cells and the anti-hyperuricemic activity in rats. The formulations exhibited nanometric size, a narrow size distribution, and a negative zeta potential, indicating their stability and uniformity. The efficient encapsulation of the sesquiterpene lactones within the liposomes emphasizes their potential for sustained release and therapeutic efficacy. Stability evaluation revealed a small decrease in the eremantholide C concentration and a remarkable stability in the goyazensolide concentration. In Caco-2 cells, the liposomes did not exert toxicity, but did exhibit an antiproliferative effect. In vivo assays demonstrated that the liposomes reduced serum uric acid levels. Our study represents an advancement in gout and hyperuricemia treatment. The liposomal formulations effectively reduced the toxicity associated with the sesquiterpene lactones while maintaining their therapeutic effects.

Spectrophotometric quantitative analysis of lesinurad using extractive acid dye reaction based on greener selective computational approach

Computational studies introduce an integral approach for finding greener methods through testing solvents for reactions and extractions. Lesinurad is a novel selective uric acid reabsorption inhibitor prescribed for the treatment of chronic gout. Computational calculations were achieved to choose the best acid dye used for sensitive visible spectrophotometric determination of lesinurad. The calculations were performed using Gaussian 03 software based on density functional theory method with B3LYP/6-31G(d) basis set. The obtained results revealed that bromophenol blue was preferred for lesinurad than other acid dyes based on the higher calculated interaction energy. The described method was based on the reaction of lesinurad with the theoretically selected acid dye bromophenol blue to form a yellow ion-pair complex. The absorption spectra showed maximum sharp peaks at 418 nm. Different factors affecting the reaction were optimized. Beer's law was demonstrated over the concentration range of 2–12 μg/mL lesinurad. The described reaction was utilized for the spectrophotometric determination of lesinurad in pure form and in the pharmaceutical preparation. The greenness of the described method was assessed using four different tools namely, the national environmental method index, the analytical eco-scale, the green analytical procedure index and the novel analytical greenness metric. The proposed method seemed to be superior to the reported HPLC method with respect to the metrics of the greenness characters.

Pharmacotherapy for gout

Background: Gout is a common disease that is mainly caused by hyperuricemia. Although it is relatively easy to treat, adherence to drug treatment and the rate at which treatment targets are met is low.Current Concepts: For the treatment of acute gout attack, colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids can be used alone or in combination depending on the severity of symptoms. To prevent gout attacks, patients are started on colchicine prior to or concurrent with treatment with uric acid–lowering drugs. The treatment is maintained until serum uric acid levels have returned to normal, and the patient has had no acute attacks for three to six months. Ultimately, the symptoms of gout are controlled in the long term by treating the patient’s hyperuricemia. For this purpose, allopurinol, febuxostat, and benzbromarone are used, and the side effects and contraindications for each drug should be checked. The goal for the treatment of chronic gout is to maintain a serum uric acid concentration below 6.0 mg/dL.Discussion and Conclusion: Patients visit the emergency departments of hospitals for sudden gout attacks. However, gout is a chronic disease that requires the lifelong use of uric acid–lowering agents. Therefore, it is necessary to educate patients on a serum urate-based treat-to-target approach.

Cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout: A systematic and meta-analysis.

The cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout remains equivocal. Febuxostat had a better safety outcome compared with allopurinol. In this systematic review and meta‐analysis, we searched MEDLINE and Embase for articles published between March 1, 2000 and April 4, 2021, without any language restrictions. We did a systematic review and meta‐analysis of included clinical trials to evaluate the cardiovascular safety of febuxostat compared to allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios were calculated with random effects and were reported with corresponding 95% confidence intervals (CI). From 240 potentially relevant citations, 224 papers were excluded; 16 studies were ultimately included in the analysis. Febuxostat had a better safety outcome compared with allopurinol，which was the composite of urgent coronary revascularization (OR: 0.84, 95% CI: 0.77–0.90, p < .0001) and stroke (OR: 0.87, 95% CI: 0.79–0.97, p = .009). However, that difference was not found in nonfatal myocardial infarction (OR: 0.99, 95% CI: 0.80–1.22, p = .91), cardiovascular related mortality (OR: 0.98, 95% CI: 0.69–1.38, p = .89) and all‐cause mortality (OR: 0.93, 95% CI: 0.75–1.15, p = .52). No significant differences in cardiovascular related mortality and all‐cause mortality were observed across any subgroup. This meta‐analysis adds new evidence regarding the cardiovascular safety of febuxostat in patients. Initiation of febuxostat in patients was not associated with an increased risk of death or serious cardiovascular related adverse events compared with allopurinol.

Režim ishrane može biti najvažni segment u terapiji uspešnog snižavanja urata kod gihta

Hyperuricemia and chronic deposition of monosodium urate crystals are the main cause of the gout. Urate lowering therapy (ULT) is the mainstay of chronic gout treatment. In this study, we evaluated demographic features and disease properties of the patients that would relate with the success of ULT. Sixty-six gout patients on pharmacologic ULT were enrolled in the study. Non-adherence to pharmacologic ULT was an exclusion criterium. Demographic and therapeutic features and co-illnesses and disease features of the patients were obtained during the study. Then, we compared these parameters between the patients with successful ULT and inadequate ULT. Adherence to diet was found different between the groups (OR, 7.00; CL%95 2.27 - 21.56). All other features including maximum allopurinol dosage were similar. We found that diet was the only factor that relate with success of ULT, while patients were on pharmacologic ULT. Non-adherence to both pharmacologic and non-pharmacologic measures is the main problem during ULT. Therefore, clinicians should emphasize the importance of all segments of ULT, including diet with informing patients during visits about the nature of disease and benefits of ULT.

Design and Optimization of Colorimetric Paper-Based Analytical Device for Rapid Detection of Allopurinol in Herbal Medicine.

Traditional herbal medicine in Indonesia is still in great demand and popular in society. The Indonesian government regulations state that herbal medicine should not contain chemical drug due to the toxic effect of uncontrolled consumption. Allopurinol is one of the drugs commonly added to herbal medicine for the treatment of chronic gout. Paper-based analytical device is one of the latest forms of analysis that has been widely used for the identification of chemical elements, environmental contamination, bacteria, and many more. In this study, experiments were conducted using Whatman filter paper No. 1, No. 2, and No. 4 and Whatman chromatography as a paper, and 9 colorimetric reagents were tested for allopurinol detection in herbal medicine. There were 5 specific reagents that reacted positively with allopurinol and only 3 reagents that can be applied to the paper, that is, Folin-Ciocalteu, Tollens, and p-DAB reagent. The results of the optimization show that the most optimal immersion time was 60 minutes with a drying time of 30 minutes at 50°C. Each filter paper has different characteristic; however, there was no significant difference when all of the papers were used as PAD for allopurinol detection.

Lesinurad: A Novel Agent for Management of Chronic Gout.

To review the pharmacology, efficacy, and safety of lesinurad and determine its role relative to other agents in the management of chronic gout. A PubMed search (1946 to February 2018) using the terms lesinurad and RDEA594 was conducted to identify relevant articles. In vitro or in vivo evaluations of lesinurad published in the English language were eligible for inclusion. Phase II and III trials were selected for review of efficacy and safety. Five clinical trials were evaluated. In 4 trials in which lesinurad was used in combination with a xanthine oxidase inhibitor (XOI), a greater percentage of patients receiving lesinurad 200 mg (54.0%-63.0%) compared with placebo (23.3%-46.8%) achieved a serum uric acid (sUA) level of <6 mg/dL at 1 to 6 months. In one trial involving lesinurad used as monotherapy, a sUA level of <6 mg/dL was achieved by a significantly greater percentage of patients receiving lesinurad 400 mg (29.9%) compared with placebo (1.9%) at 6 months. When used as combination therapy, the drug had an acceptable safety profile, with upper-respiratory-tract infection, nasopharyngitis, and hypertension occurring most commonly and transient renal-related events detected less frequently. Lesinurad has a novel mechanism of action and is safe and effective for the treatment of chronic gout. At this time, lesinurad may be considered as an add-on therapy for patients who have an inadequate response to maximum tolerated doses of a XOI.

Second derivative spectrophotometric and synchronous spectrofluorometric determination of lesinurad in the presence of its oxidative degradation product

Lesinurad is a novel selective uric acid reabsorption inhibitor which has been recently approved for the treatment of chronic gout.

Allopurinol for chronic gout.

Allopurinol for chronic gout.

Physician Adherence to ACR Gout Treatment Guidelines: Perception Versus Practice

Background: In October 2012, the American College of Rheumatology (ACR) published recommendations for chronic gout treatment goals and pharmacotherapy. Objectives: Identify potential gaps between real-world chronic gout treatment, ACR guideline recommendations, and physicians' perceived guideline adherence by evaluating records of patients classified as having “higher” and “lower” guideline adherence as defined by the investigators. Methods: A comprehensive quantitative survey was administered between February 11 and February 22, 2013, to physicians treating patients with gout; the survey included a patient record chart review informed by prior qualitative interviews. Eight criteria from the ACR gout management guidelines were used to compose the survey. To assess ACR guideline adherence, information from records of patients with chronic gout treated by primary care physicians (PCPs) and rheumatologists was scored from 0 (no adherence) to 8 (total adherence), in accordance with ACR guideline recommendations. Physicians also indicated how closely they believed patient treatment followed current guidelines on a 10-point scale. Results: Of the 350 records of patients with chronic gout, all but 3 PCP patients were adherent on ≥ 1 guideline recommendation, but nearly all patients could be considered nonadherent, considering all potential recommendations. Patients with chronic gout treated by rheumatologists tended to be managed more closely to ACR guidelines than patients treated by PCPs (mean scores: rheumatologists 5.8/8 ± 1.7 vs 4.3/8 ± 1.7 for PCPs). Among patients classified as having “higher adherence” based on adherence scores, there was low adherence on first-line urate lowering therapy dose, acute prophylaxis dosing, and length of prophylaxis treatment. Among PCPs and rheumatologists, there was a disparity between how closely physicians believed patient treatment followed guidelines and actual adherence with ACR guidelines based on adherence scores. For 16.4% of patients treated by PCPs and 18.4% of patients seen by rheumatologists, physicians believed they closely followed ACR guidelines (score of 8–10/10) for each patient; but in actuality, adherence was lower. Conclusion: Although adherence with ACR guidelines is higher among rheumatologists than PCPs in treating patients with gout, overall adherence could be improved by both specialties.

A systematic review and meta-analysis on the safety and efficacy of febuxostat versus allopurinol in chronic gout

ObjectiveTo evaluate the safety and efficacy of febuxostat compared to allopurinol for the treatment of chronic gout. MethodsWe did a systematic review and meta-analysis of randomized and non-randomized controlled trials that compared oral febuxostat to oral allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios (RR) were calculated with random effects and were reported with corresponding 95% confidence intervals (CI). ResultsFrom 1076 potentially relevant citations, 7 studies and 25 associated publications met inclusion criteria; 5 studies were ultimately included in the analysis. Febuxostat did not reduce the risk of gout flares compared with allopurinol (RR = 1.16, 95% CI = 1.03–1.30, I2 = 44%). Overall, the risk of any adverse event was lower in febuxostat recipients compared to allopurinol (RR = 0.94, 95% CI = 0.90–0.99, I2 = 13%). Patients receiving febuxostat were more likely to achieve a serum uric acid of <6mg/dl than allopurinol recipients (RR = 1.56, 95% CI = 1.22–2.00, I2 = 92%). Subgroup analysis did not indicate any significant difference between high- and low-dose febuxostat on the risk of gout flares. ConclusionAlthough febuxostat was associated with higher likelihood of achieving a target serum uric acid level of <6mg/dl, there was significant heterogeneity in the pooled results. There was no evidence that febuxostat is superior to allopurinol for clinically relevant outcomes. Given its higher cost, febuxostat should not be routinely used for chronic gout.

Benefit restrictions and gout treatment.

Gout is a chronic rheumatic disease that can have serious sequelae, including persistent pain, nerve compression, joint destruction and deformities if left untreated. Febuxostat, initially introduced in the United States in 2009, was the first new treatment option for gout in over 40 years. With the introduction of a new drug into a therapeutic class that is composed of generically available options, utilization management will be a common strategy employed in an effort to contain cost; however, the effects of these strategies are not known for chronic gout treatment. To evaluate the effect of utilization management strategies on chronic gout treatment. This retrospective analysis examined claims data from a large, national pharmacy benefits manager with a client base that includes commercial HMOs, Medicaid, Medicare Part D, and self-insurers. The study population included patients aged 18 years or older who had at least 1 rejected claim for febuxostat in the 16-month identification period from March 1, 2009, through June 30, 2010. Outcomes of interest were the proportion of patients who filled a febuxostat prescription and proportion of patients who filled a prescription for another chronic gout treatment within 1 month of the febuxostat claim rejection date (the index date). Multivariate logistic regression models were used to assess factors affecting patient response to a rejected febuxostat claim. Of 1,034 patients with rejected febuxostat claims, 95% had claims denied due to utilization management: 36% due to step therapy, 25% due to lack of drug coverage, 18% due to quantity or other limits (i.e., fill limit exceeded, days supply exceeding benefit maximum, or maximum days supply limit exceeded), 16% due to prior authorization requirements, while 5% were due to "other reasons" unrelated to the utilization management strategies of interest. "Other reasons" included over 100 possible rejection reasons such as fill dispensed too soon, missing/invalid days supply, group not having benefit, physician not covered, non-matched group, not a network pharmacy, non-matched member, claim/member birth date not matching, and missing/invalid prescriber identifier. Subsequently, 474 (46%) of these patients filled a febuxostat prescription within 1 month of a rejected claim; 364 (35%) had not filled a prescription for any chronic gout medication within a month of the febuxostat claim rejection. Those filling a febuxostat prescription had higher pre-index total 6-month pharmacy costs than those not filling a chronic gout prescription ($1,718 vs. $988; P < 0.001) . They also had a higher number of pre-index drug claims (25 vs. 18; P < 0.001). The regression model found the following variables to be statistically significant in positively influencing the likelihood of patients filling a febuxostat prescription within a month of a febuxostat claim rejection: (a) self-insured coverage (compared with commercial HMO coverage); (b) pre-index total prescription costs of at least $1,800; (c) claim rejection due to quantity or other limit (compared with lack of drug coverage); (d) claim rejection due to "other reason" (compared with lack of drug coverage); and (e) 1 and ≥1 pre-index colchicine claim. Patients with projected febuxostat copay of $100 to $149 were found to be less likely to fill febuxostat compared with patients with a projected copay of $0 to $19. Utilization management strategies likely result in gaps in gout treatment; 35% of patients with a denied febuxostat claim in this study population did not fill a prescription for any chronic gout therapy within a month of the claim denial. These findings are important in the consideration of benefit design in gout treatment.

SP0007 Chronic Gout, Chronic Treatment

Gout is a chronic metabolic and inflammatory disease whose sine qua non is hyperuricemia. The acute attacks seen in gout are merely the “tip of the iceberg” and represent the...

Febuxostat for treating chronic gout

Gout is the most common inflammatory arthritis in men over 40 years and has an increasing prevalence among postmenopausal women. Lowering serum uric acid levels remains one of the primary goals in the treatment of chronic gout. In clinical trials, febuxostat has been shown to be effective in lowering serum uric acid levels to < 6.0 mg/dL. To evaluate the benefits and harms of febuxostat for chronic gout. We searched The Cochrane Library, MEDLINE, EMBASE, and International Pharmaceutical Abstracts from inception to July 2011. The ClinicalTrials.gov website was searched for references to trials of febuxostat. Our search did not include any restrictions. Two authors independently reviewed the search results and disagreements were resolved by discussion. We included any controlled clinical trial or open label trial (OLT) using febuxostat at any dose. Data and risk of bias were independently extracted by two authors and summarised in a meta-analysis. Continuous data were expressed as mean difference and dichotomous data as risk ratio (RR). Four randomised trials and two OLTs with 3978 patients were included. Risk of bias differed by outcome, ranging from low to high risk of bias. Included studies failed to report on five to six of the nine outcome measures recommended by OMERACT. Patients taking febuxostat 120 mg and 240 mg reported more frequent gout flares than in the placebo group at 4 to 28 weeks (RR 1.7; 95% CI 1.3 to 2.3, and RR 2.6; 95% CI 1.8 to 3.7 respectively). No statistically significant differences were observed at 40 mg and 80 mg. Compared to placebo, patients on febuxostat 40 mg were 40.1 times more likely to achieve serum uric acid levels < 6.0 mg/dL at 4 weeks (95% CI 2.5 to 639), with an absolute treatment benefit of 56% (95% CI 37% to 71%). For febuxostat 80 mg and 120 mg, patients were 68.9 and 80.7 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit compared to placebo (95% CI 13.8 to 343.9, 95% CI 16.0 to 405.5), respectively; with an absolute treatment benefit of 75% and 87% (95% CI 68 to 80% and 81 to 91%), respectively. Total discontinuation rates were significantly higher in the febuxostat 80 mg group compared to placebo (RR 1.4; 95% CI 1.0 to 2.0, absolute risk increase 11%; 95% CI 3 to 19%). No other differences were observed.When comparing allopurinol to febuxostat at 24 to 52 weeks, the number of gout flares was not significantly different between the two groups, except for febuxostat 240 mg (RR 2.3; 95% CI 1.7 to 3.0). Patients on febuxostat 40 mg showed no statistically significant differences in benefits or harms. Patients on febuxostat 80 mg and 120 mg were 1.8 and 2.2 times more likely to achieve serum uric acid levels < 6.0 mg/dL at their final visit (95% CI 1.6 to 2.2, 95% CI 1.9 to 2.5) with an absolute treatment benefit of 29% and 44% (95% CI 25% to 33%, 95% CI 38% to 50%), respectively, at 24 to 52 weeks. Total discontinuation rates were higher for febuxostat 80 mg and 120 mg compared to allopurinol (RR 1.5; 95% CI 1.2 to 1.8, absolute risk increase 11%; 95% CI 6% to 16%; and RR 2.6; 95% CI 2.0 to 3.3, absolute risk increase 20%; 95% CI 3% to 14%, respectively). Discontinuations due to adverse events were similar across groups. Total adverse events were lower for febuxostat 80 mg and 120 mg compared with allopurinol (RR 0.93; 95% CI 0.87 to 0.99, absolute risk increase 6%; 95% CI 0.7% to 11%; and RR 0.90; 95% CI 0.84 to 0.96, absolute risk increase 8%; 95% CI 3% to 13%, respectively). No other relevant differences were noted.After 3 years of follow-up there were no statistically significant differences regarding effectiveness and harms between febuxostat 80 mg or 120 mg and allopurinol groups (adverse event rate per 100 patient-years 227, 216, and 246, respectively). Although the incidence of gout flares requiring treatment may be increased in patients taking febuxostat compared to placebo or allopurinol during early treatment, no such increase in gout flares was observed in the long-term follow-up study when compared to allopurinol. Febuxostat at any dose was shown to be beneficial in achieving serum uric acid levels < 6.0 mg/dL and reducing serum uric acid levels in the period from baseline to final visit when compared to placebo and to allopurinol. However, the grade of evidence ranged from low to high, which indicates that further research is needed.

Pegloticase: a new biologic for treating advanced gout

Although pharmacologic therapies for hyperuricemia in patients with gout have been well established and are reasonably effective, a small proportion of patients are refractory to treatment and/or present with articular disease so severe as to render standard treatments inadequate. Pegloticase, a PEGylated mammalian urate oxidase with a novel mechanism of action, was recently approved in the USA for the treatment of chronic gout in adult patients refractory to conventional therapy. This paper outlines the development of this unique agent and provides details of the Phase III clinical trial program. A discussion of patient selection, treatment considerations, and risk management for infused pegloticase follows. As a new class of biologic agent offering documented and dramatic effects on lowering serum uric acid and remarkably rapid outcomes in resolving tophi, pegloticase can provide safe and effective management of hyperuricemia and gout for many patients, particularly those who have a high disease burden ...

Physicochemical characterization and solubility enhancement studies of allopurinol solid dispersions

Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with treatment of diuretic conditions. One of the major problems with the drug is that it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation, kneading method, co-precipitation method, co-grinding method and closed melting methods to increase its water solubility. Hydrophilic carriers such as polyvinylpyrrolidone, polyethylene glycol 6000 were used in the ratio of 1:1, 1:2 and 1:4 (drug to carrier ratio). The aqueous solubility of allopurinol was favored by the presence of both polymers. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, powder X-ray diffraction, UV and Fourier Transform Infrared spectroscopy. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure allopurinol, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. Solid dispersion prepared with polyvinylpyrrolidone showed highest improvement in wettability and dissolution rate of allopurinol. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the present study showed that polyvinylpyrrolidone and polyethylene glycol 6000 have a significant solubilizing effect on allopurinol.

Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment

Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. clinicaltrials.gov Identifier: NCT00325195.

Febuxostat for treatment of chronic gout

The pharmacology, pharmacokinetics, clinical efficacy, and safety of febuxostat are reviewed. Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase for the management of hyperuricemia in patients with gout. The ability of febuxostat to decrease serum uric acid production through selective inhibition of enzyme xanthine oxidase has been established in short-term Phase II and III clinical trials and long-term open-label studies. Clinical studies have revealed that febuxostat lowers serum uric acid levels more potently than allopurinol while having minimal effects on other enzymes associated with purine and pyrimide metabolism. The most frequent adverse events reported in clinical trials with febuxostat were liver function abnormalities, nausea, arthralgias, and rash. More cardiovascular thromboembolic events occurred in randomized trials in patients treated with febuxostat. Although a causal relationship has not been established, patients should be monitored for signs and symptoms of myocardial infarction and stroke. Febuxostat is available as 40- and 80-mg tablets. The recommended starting dosage is 40 mg orally once daily. If serum uric acid concentrations are not less than 6 mg/dL after two weeks, the dosage can be increased to 80 mg orally once daily. Dosage adjustments are not needed in elderly patients or patients with mild or moderate renal or hepatic impairment. Febuxostat is efficacious as a second-line therapy in lowering serum uric acid levels in patients with gout. Febuxostat may be an alternative for patients with gout who are unable to take allopurinol due to hypersensitivity, intolerance, or lack of efficacy.

Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials

Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials

Preparation and in vitro evaluation of Allopurinol-Gelucire 50/13 solid dispersions.

The rate-limiting step to absorption of drugs from the gastrointestinal tract is often dissolution from the dosage form. Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with leukaemia, radiotherapy, anti-neoplastic agents. One of the major problems with allopurinol is that, it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation method, kneading method, co-precipitation method, co-grinding method and closed melting method to increase its water solubility. In the present study amphiphilic carrier like gelucire 50/13 was used in the ratio of 1:1, 1:2 and 1:4. Prepared solid dispersions were characterized in the liquid state by phase solubility studies and in the solid state by Differential Scanning calorimetric analysis, Powder X-ray diffractometry and Fourier Transform Infrared spectroscopy. The aqueous solubility of allopurinol was preferential by the presence polymer with increasing concentration. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix.Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the current study showed that gelucire 50/13 has a significant solubilizing effect on allopurinol. Keywords: Allopurinol, gelucire 50/13, closed melting-method, co-grinding, dissolution study, powder X-ray diffraction analysis