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Arthritis Care & Research Jun 2024We sought to evaluate urate-lowering therapy (ULT) adherence and treatment-to-target (T2T) serum uric acid (SUA) levels among older adults with gout starting ULT.
OBJECTIVE
We sought to evaluate urate-lowering therapy (ULT) adherence and treatment-to-target (T2T) serum uric acid (SUA) levels among older adults with gout starting ULT.
METHODS
We performed a population-based retrospective cohort study in Ontario, Canada in patients with gout aged ≥66 years newly dispensed ULT between 2010 and 2019. We defined successful T2T as patients having SUA levels <360 μmol/L (6 mg/dL) within 12 months after ULT dispensation. We also assessed adherence to ULT. Multilevel logistic regression clustered by ULT prescriber evaluated patient, physician, and prescription factors associated with reaching target SUA levels.
RESULTS
Among 44,438 patients (mean ± SD age 76.0 ± 7.3 years; 64.4% male), 30,057 (67.6%) patients had ≥1 SUA test completed. Overall, 52.3% patients reached SUA target within 12 months, improving from 45.2% in 2010 to 61.2% in 2019 (P < 0.0001). ULT adherence was 55.3% overall and improved annually. Key factors associated with achieving T2T included febuxostat treatment (odds ratio [OR] 11.40, 95% confidence interval [95% CI] 5.10-25.43) (was only dispensed in 88 patients), ULT adherence (OR 5.17, 95% CI 4.89-5.47), allopurinol starting doses >50 mg (OR 2.53, 95% CI 2.14-2.99), colchicine/oral glucocorticoids co-prescription (OR 1.24, 95% CI 1.14-1.34), and ULT prescription from a rheumatologist.
CONCLUSION
Only 52.3% of patients achieved an optimal SUA level within 1 year of ULT initiation. ULT adherence was suboptimal, although improving over time. ULT adherence and higher allopurinol starting doses had the strongest associations of achieving a target SUA level. This study highlights room for improvement in gout management and potential strategies to address care gaps.
PubMed: 38831665
DOI: 10.1002/acr.25380 -
Phytochemistry Aug 2024Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the...
Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC = 11.1 μM) with IC values of 1.0 μM, and 2.5 μM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.
Topics: Xanthine Oxidase; Rubiaceae; Structure-Activity Relationship; Indole Alkaloids; Enzyme Inhibitors; Monoterpenes; Molecular Structure; Dose-Response Relationship, Drug; Models, Molecular; Crystallography, X-Ray
PubMed: 38825030
DOI: 10.1016/j.phytochem.2024.114169 -
Chemico-biological Interactions Jul 2024Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to...
Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects. Our study focuses on Asphodelus microcarpus, a plant renowned for traditional anti-inflammatory uses. Recent investigations into its phenolic-rich flowers, notably abundant in luteolin derivatives, reveal its potential as a natural source of XO inhibitors. In the present research, XO inhibition by an ethanolic flowers extract from A. microcarpus is reported. In silico docking studies have highlighted luteolin derivatives as potential XO inhibitors, and molecular dynamics support that luteolin 7-O-glucoside has the highest binding stability compared to other compounds and controls. In vitro studies confirm that luteolin 7-O-glucoside inhibits XO more effectively than the standard inhibitor allopurinol, with an IC value of 4.8 μg/mL compared to 11.5 μg/mL, respectively. These findings underscore the potential therapeutic significance of A. microcarpus in managing conditions related to XO activity. The research contributes valuable insights into the health-promoting properties of A. microcarpus and its potential application in natural medicine, presenting a promising avenue for further exploration in disease management.
Topics: Xanthine Oxidase; Enzyme Inhibitors; Molecular Docking Simulation; Luteolin; Plant Extracts; Glucosides; Molecular Dynamics Simulation; Flowers; Allopurinol; Humans; Binding Sites
PubMed: 38823536
DOI: 10.1016/j.cbi.2024.111087 -
The American Journal of Medicine Jun 2024
Topics: Humans; Allopurinol; Liver Cirrhosis
PubMed: 38821688
DOI: 10.1016/j.amjmed.2024.01.032 -
Expert Opinion on Drug Metabolism &... Jun 2024In addition to the well-established understanding of the pharmacogenetics of drug-metabolizing enzymes, there is growing data on the effects of genetic variation in drug... (Review)
Review
INTRODUCTION
In addition to the well-established understanding of the pharmacogenetics of drug-metabolizing enzymes, there is growing data on the effects of genetic variation in drug transporters, particularly ATP-binding cassette (ABC) transporters. However, the evidence that these genetic variants can be used to predict drug effects and to adjust individual dosing to avoid adverse events is still limited.
AREAS COVERED
This review presents a summary of the current literature from the PubMed database as of February 2024 regarding the impact of genetic variants on ABCG2 function and their relevance to the clinical use of the HMG-CoA reductase inhibitor rosuvastatin and the xanthine oxidase inhibitor allopurinol.
EXPERT OPINION
Although there are pharmacogenetic guidelines for the ABCG2 missense variant Q141K, there is still some conflicting data regarding the clinical benefits of these recommendations. Some caution appears to be warranted in homozygous ABCG2 Q141K carriers when rosuvastatin is administered at higher doses and such information is already included in the drug label. The benefit of dose adaption to lower possible side effects needs to be evaluated in prospective clinical studies.
Topics: Humans; ATP Binding Cassette Transporter, Subfamily G, Member 2; Rosuvastatin Calcium; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neoplasm Proteins; Allopurinol; Pharmacogenetics; Polymorphism, Genetic; Dose-Response Relationship, Drug; Enzyme Inhibitors; Animals; Mutation, Missense
PubMed: 38809523
DOI: 10.1080/17425255.2024.2362184 -
Acta Tropica Aug 2024Chagas disease (CD), caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), affects approximately 7 million people worldwide and is endemic in Latin America,... (Review)
Review
Chagas disease (CD), caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), affects approximately 7 million people worldwide and is endemic in Latin America, especially among socioeconomically disadvantaged populations. Since the 1960s, only two drugs have been commercially available for treating this illness: nifurtimox (NFX) and benznidazole (BZN). Although these drugs are effective in the acute phase (AP) of the disease, in which parasitemia is usually high, their cure rates in the chronic phase (CP) are low and often associated with several side effects. The CP is characterized by a subpatent parasitaemia and absence of clinical symptoms in the great majority of infected individuals. However, at least 30 % of the individuals will develop potentially lethal symptomatic forms, including cardiac and digestive manifestations. For such reason, in the CP the treatment is usually symptomatic and typically focuses on managing complications such as arrhythmias, heart failure, or digestive problems. Therefore, the need for new drugs or therapeutic approaches using BZN or NFX is extremely urgent. This review presents the main clinical trials, especially in the CP, which involve BZN and NFX in different treatment regimens. Additionally, other therapies using combinations of these drugs with other substances such as allopurinol, itraconazole, ravuconazole, ketoconazole, posaconazole and amiodarone are also reported. The importance of early diagnosis, especially in pediatric patients, is also discussed, emphasizing the need to identify the disease in its early stages to improve the chances of successful treatment.
Topics: Chagas Disease; Humans; Nitroimidazoles; Trypanosoma cruzi; Trypanocidal Agents; Nifurtimox; Chronic Disease
PubMed: 38806090
DOI: 10.1016/j.actatropica.2024.107264 -
Journal of Oncology Pharmacy Practice :... May 2024This study aimed to characterize rasburicase dosing and duration. Secondary objectives included characterizing the indication of rasburicase and identifying the...
PURPOSE
This study aimed to characterize rasburicase dosing and duration. Secondary objectives included characterizing the indication of rasburicase and identifying the utilization of prophylactic therapy for tumor lysis syndrome (TLS).
METHODS
This retrospective review included patients 0 to 89 years old admitted between 1 January 2021 and 31 December 2021, and received at least one dose of rasburicase. Patients were excluded if they were >89 years old, pregnant, lactating, or received rasburicase outpatient.
RESULTS
A total of 192 patients, 176 adults and 16 pediatric patients were included in the retrospective review. Of the total population, 184 received a fixed dose of rasburicase and 8 patients received a weight-based dose (0.15 mg/kg/dose) of rasburicase. The average dose administered was 3.4 mg for fixed and 2.99 mg for weight-based dosing. Nearly half (49.5%) the patients received rasburicase for an elevated uric acid but did not meet Cairo-Bishop criteria for TLS. Only 42.2% received at least one dose of allopurinol within 5 days prior to rasburicase and 18.8% received aggressive hydration within 72 h prior to rasburicase.
CONCLUSION
The majority of rasburicase administered was ordered as fixed dose for a uric acid level ≥7.5 mg/dL. Most patients did not meet criteria for laboratory or clinical TLS and less than half the patients received prophylactic allopurinol and/or aggressive hydration. These study results are supported by recent literature for fixed dose rasburicase as a safe and economical dosing strategy compared to weight-based dosing.
PubMed: 38794946
DOI: 10.1177/10781552241253214 -
Animals : An Open Access Journal From... May 2024Leishmaniasis in wild canids is a vector-borne disease caused in Europe by the protozoan parasite . To date, there is limited information on clinical signs and...
Leishmaniasis in wild canids is a vector-borne disease caused in Europe by the protozoan parasite . To date, there is limited information on clinical signs and laboratory abnormalities in wolves due to leishmaniasis. The current clinical case report described a female Iberian wolf () housed in semi-captivity conditions at the Centro del Lobo Ibérico "Félix Rodríguez de la Fuente", in Robledo de Sanabria, Zamora (Spain), with an interdigital ulcerous wound at the right forepaw, hyper-gammaglobulinemia, and abnormal liver blood parameters. Definitive serodiagnosis of leishmaniasis was established using antileishmanial serum antibodies and PCR analysis of different biological samples. A gold-standard anti- treatment protocol consisting in subcutaneous meglumine antimoniate and oral allopurinol combination was installed. However, the presence of pain at the site of injection due to meglumine antimoniate administration forced its substitution by oral miltefosine. A progressive reduction of the levels of anti- serum antibodies and the concentrations of gamma-globulin fraction was detected after antileishmanial treatment as well as a decline of liver GPT. To our knowledge, this is the first case of leishmaniasis diagnosed in a wolf housed in semi-captivity conditions, with the condition subsequently treated and successfully cured.
PubMed: 38791654
DOI: 10.3390/ani14101436 -
Metabolites May 2024Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, and coenzyme A, are essential molecules in...
Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, and coenzyme A, are essential molecules in diverse biological processes such as energy metabolism, signal transduction, and enzyme activity. When purine levels increase, excess purines are either recycled to synthesize purine metabolites or catabolized to the end product uric acid. Purine catabolism increases during states of low oxygen tension (hypoxia and ischemia), but this metabolic pathway is incompletely understood in the context of histotoxic hypoxia (i.e., inhibition of oxygen utilization despite normal oxygen tension). In rabbits exposed to cyanide-a classical histotoxic hypoxia agent-we demonstrated significant increases in several concordant metabolites in the purine catabolic pathway (including plasma levels of uric acid, xanthosine, xanthine, hypoxanthine, and inosine) via mass spectrometry-based metabolite profiling. Pharmacological inhibition of the purine catabolic pathway with oxypurinol mitigated the deleterious effects of cyanide on skeletal muscle cytochrome c oxidase redox state, measured by non-invasive diffuse optical spectroscopy. Finally, plasma uric acid levels correlated strongly with those of lactic acid, an established clinical biomarker of cyanide exposure, in addition to a tissue biomarker of cyanide exposure (skeletal muscle cytochrome c oxidase redox state). Cumulatively, these findings not only shed light on the in vivo role(s) of cyanide but also have implications in the field of medical countermeasure (MCM) development.
PubMed: 38786756
DOI: 10.3390/metabo14050279 -
Cardiology Journal 2024Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between... (Meta-Analysis)
Meta-Analysis
Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between urate-lowering therapy and all-cause mortality in different chronic diseases to match its users and non-users in a real-world setting. Overall, 11 studies were included, which reported adjusted hazard ratios for all-cause mortality over at least 12 months. Meta-analysis of all included studies showed no effect of the therapy on all-cause mortality. However, subgroup analyses showed its beneficial effect in patients with chronic kidney disease (14% risk reduction) and hyperuricemia (14% risk reduction), but not in patients with heart failure (28% risk increase). Urate-lowering therapy reduces all-cause mortality among patients with hyperuricemia and chronic kidney disease, but it seems to increase mortality in patients with heart failure and should be avoided in this subgroup.
Topics: Humans; Xanthine Oxidase; Hyperuricemia; Cause of Death; Enzyme Inhibitors; Risk Factors; Allopurinol; Gout Suppressants; Febuxostat; Heart Failure; Uric Acid; Renal Insufficiency, Chronic; Adult
PubMed: 38771265
DOI: 10.5603/cj.97807