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Pediatric Hematology and Oncology Jun 2024This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective...
This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective observational study of pediatric leukemia patients admitted between 2009-2019 at a single-center academic children's hospital was conducted to determine PGx-drug exposure within 3 years of diagnosis. Along with baseline demographic and clinical characteristics of these patients, data regarding dates of diagnosis, relapse, death were collected. During the study period, inclusion criteria were met by 714 patients. The most frequently given medications were ondansetron (96.1%), morphine (92.2%), and allopurinol (85.3%) during the study period. In this cohort, 82% of patients received five or more PGx-drugs. Patients diagnosed with acute myeloid leukemia and leukemia unspecified were prescribed more PGx-drugs than other types of leukemia. There was a significant relationship between age at diagnosis and the number of PGx-drugs prescribed. Adolescents and adults both received a median of 10 PGx-drugs, children received a median of 6 PGx-drugs, and infants received a median of 7 PGx-drugs ( < 0.001). Patients with recurrent leukemia had significantly more PGx-drugs prescribed compared to those without recurrent disease, 10 drugs and 6 drugs, respectively ( < 0.001). Patients diagnosed with childhood leukemia are high utilizers of PGx-drugs. There is a vital need to understand how PGx testing may be utilized to optimize treatment and enhance quality of life. Preemptive PGx testing is a tool that aids in optimization of drug therapy and decreases the need for later treatment modifications. This can result in financial savings from decreased health-care encounters.
PubMed: 38904214
DOI: 10.1080/08880018.2024.2368007 -
Molecules (Basel, Switzerland) May 2024Taste sensors with an allostery approach have been studied to detect non-charged bitter substances, such as xanthine derivatives, used in foods (e.g., caffeine) or...
Taste sensors with an allostery approach have been studied to detect non-charged bitter substances, such as xanthine derivatives, used in foods (e.g., caffeine) or pharmaceuticals (e.g., etofylline). In this study, the authors modified a taste sensor with 3-bromo-2,6-dihydroxybenzoic acid and used it in conjunction with sensory tests to assess the bitterness of non-charged pharmaceuticals with xanthine scaffolds (i.e., acefylline and doxofylline), as well as allopurinol, an analogue of hypoxanthine. The results show that the sensor was able to differentiate between different levels of sample bitterness. For instance, when assessing a 30 mM sample solution, the sensor response to acefylline was 34.24 mV, which corresponded to the highest level of bitterness (τ = 3.50), while the response to allopurinol was lowest at 2.72 mV, corresponding to relatively weaker bitterness (τ = 0.50). Additionally, this study extended the application of the sensor to detect pentoxifylline, an active pharmaceutical ingredient in pediatric medicines. These results underscore the taste sensor's value as an additional tool for early-stage assessment and prediction of bitterness in non-charged pharmaceuticals.
Topics: Allopurinol; Taste; Humans; Xanthine; Biosensing Techniques
PubMed: 38893328
DOI: 10.3390/molecules29112452 -
ARYA Atherosclerosis 2023The generation of reactive oxygen species, which is induced by the activation of the xanthine oxidase (XO) enzymatic system, is one of the primary causes of...
Impact of Allopurinol Pretreatment on Coronary Blood Flow and Revascularization Outcomes after Percutaneous Coronary Intervention in Acute STEMI Patients: A Randomized Double Blind Clinical Trial.
INTRODUCTION
The generation of reactive oxygen species, which is induced by the activation of the xanthine oxidase (XO) enzymatic system, is one of the primary causes of ischemia-reperfusion injury for an ischemic heart. Allopurinol, as an XO inhibitor, plays an inhibitory role in free radical production in ST-elevation myocardial infarction (STEMI) patients. The aim of this study is to evaluate the impact of allopurinol pre-treatment on post-revascularization outcomes in patients admitted with STEMI.
METHOD
Ninety patients with acute STEMI were enrolled in this randomized double-blind clinical trial and divided into two equal groups. The allopurinol group received a 600 mg allopurinol loading dose before the emergency PCI, and the control group received a placebo medication of the same shape. Thrombolysis in Myocardial Infarction (TIMI) flow, ECG changes, troponin level, and the occurrence of major cardiac events (MACE) during a 1-month follow-up were assessed.
RESULTS
In the end, 81 patients were analyzed. The mean age of the patients was 59.52(11.31) and 61.3(9.25) in the allopurinol and control groups, respectively (p = 0.49). The troponin level 48 hours after the PCI and ST-elevation regression showed no significant difference between the groups [(p = 0.25) and (p = 0.21), respectively]. TIMI flow had improved in the allopurinol group compared to the placebo (p = 0.02). The PCI success rate was 78.6% and 61.5% in the case and control groups, respectively (p = 0.09). MACE and other clinical outcomes were similar between the groups (p > 0.05).
CONCLUSION
This study revealed that allopurinol pre-treatment could improve TIMI flow in patients undergoing primary or rescue PCI in an acute STEMI setting.
PubMed: 38883850
DOI: 10.48305/arya.2023.11577.2121 -
ARYA Atherosclerosis Jul 2023The use of allopurinol has shown promising outcomes in reducing oxidative processes responsible for atherogenic-related cardiovascular events. The current study aims to...
The Effect of High-dose Allopurinol Pretreatment on Inflammatory Biomarkers and Post-revascularization Coronary Blood Flow in Non-STEMI Patients: A Randomized Double Blind Clinical Trial.
INTRODUCTION
The use of allopurinol has shown promising outcomes in reducing oxidative processes responsible for atherogenic-related cardiovascular events. The current study aims to assess the effects of high-dose allopurinol on the post-revascularization coronary blood flow and inflammatory biomarkers in patients with non-ST segment elevated myocardial infarction (NSTEMI).
METHOD
Eighty NSTEMI patients were randomly divided into two groups: the intervention group (n=40), medicated with a high loading dose of 600 mg allopurinol before the coronary angiography, and the control group (n=40), treated with a placebo. The highly sensitive C-reactive protein (hs-CRP) was measured at baseline and within 24 hours after the cardiac interventions and compared between the case and control groups. Post percutaneous coronary intervention (PCI) Thrombolysis in Myocardial Infarction (TIMI) flow grading was also evaluated as a revascularization endpoint.
RESULTS
The two groups of the study were similar in terms of demographic, clinical, laboratory, and angiographic characteristics (P-value>0.050). The assessed TIMI flow was similar between the cases and the controls both prior to (P-value=0.141) and after (P-value=0.395) the coronary angioplasty. The hs-CRP (P-value=0.016) was significantly higher in the control group. Post-angiographic assessment of hs-CRP revealed an insignificant difference between the groups (P-value=0.104).
CONCLUSION
In conclusion, premedication with a high dose of allopurinol in NSTEMI patients did not affect the inflammatory biomarker or the revascularization endpoint.
PubMed: 38881997
DOI: 10.48305/arya.2022.11886.2722 -
Frontiers in Medicine 2024Hyperuricemia is a common complication of hematologic malignancies, and hyperuricosuria in this population has shown conflicting results. This study aimed to determine...
INTRODUCTION
Hyperuricemia is a common complication of hematologic malignancies, and hyperuricosuria in this population has shown conflicting results. This study aimed to determine the prevalence of hyperuricemia and parameters associated with serum uric acid (SUA) and urine uric acid (UUA) in patients with lymphoma and myeloproliferative neoplasms (MPN).
METHODS
This cross-sectional study included adult patients with newly diagnosed lymphoma and MPN at the university-based hospital. Clinical characteristics were collected, and independent risk factors for hyperuricemia and hyperuricosuria were determined using multiple logistic regression.
RESULTS
One hundred and sixty-five patients were included with a median age of 55 years (45.5-64) and 51.5% were males. There were 91 patients (55.2%) with lymphoma and 74 cases (44.8%) of MPN. Overall, hyperuricemia was prevalent in 43.6% with a median SUA of 6.3 mg/dl (4.6-8) and hyperuricosuria was detected in 39.4% with a median 24-h UUA of 545 mg (365.4-991). Hyperuricemia was observed in patients with lymphoma and MPN in 20.9% and 71.6%, respectively, and hyperuricosuria in 15.4% and 68.9%, respectively. In lymphoma patients, estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m and serum lactate dehydrogenase (LDH) ≥ 250 U/L were associated with hyperuricemia with odds ratio (OR) 3.24, 95% confidence interval (CI) 1.95-11.07, = 0.006 and OR 2.07, 95%CI 1.62-6.97, = 0.039), and only elevated serum LDH was related to hyperuricosuria (OR 2.37, 95%CI 1.56-14.29, = 0.036). In MPN patients, hemoglobin levels <10 g/dl and serum LDH ≥ 640 mg/dl were independent risk factors of hyperuricosuria (OR 1.88, 95%CI 1.42-8.39, = 0.045 and OR 6.21, 95%CI 1.49-25.74, = 0.012).
CONCLUSION
Hyperuricemia in patients with hematologic malignancies was common, notably MPN, and parameters associated with hyperuricosuria were provided. In addition to the utilization of allopurinol in patients at high risk of tumor lysis syndrome, patients without hyperuricosuria may also be of significant interest.
PubMed: 38873194
DOI: 10.3389/fmed.2024.1343000 -
Clinical Case Reports Jun 2024Hyperuricemic patients (≥7.8 mg/dL) can develop polyarticular tophaceous gout from intermittent arthritis if untreated. Acute flares and tophi development can be...
Hyperuricemic patients (≥7.8 mg/dL) can develop polyarticular tophaceous gout from intermittent arthritis if untreated. Acute flares and tophi development can be avoided by lowering blood urate levels with xanthine oxidase inhibitors.
PubMed: 38868124
DOI: 10.1002/ccr3.9033 -
Medical Science Monitor : International... Jun 2024BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering... (Observational Study)
Observational Study Comparative Study
BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.
Topics: Humans; Febuxostat; Allopurinol; Male; Female; Renal Insufficiency, Chronic; Middle Aged; Aged; Retrospective Studies; Cardiovascular Diseases; Taiwan; Hyperuricemia; Gout Suppressants; Diabetes Mellitus; Risk Factors; Adult; Hospitalization
PubMed: 38865287
DOI: 10.12659/MSM.944314 -
Journal of Cardiovascular Translational... Jun 2024Hyperuricemia is a common metabolic disorder with severe complications. We aimed to develop a mouse model for spontaneous hyperuricemia. Uox mouse model was generated on...
Hyperuricemia is a common metabolic disorder with severe complications. We aimed to develop a mouse model for spontaneous hyperuricemia. Uox mouse model was generated on C57BL/6J background by deleting exon 2-4 of Uox using the CRISPR/Cas9 system. The prototypic Uox mice had 5.5-fold increased serum uric acid (1351.04±276.58μmol/L) as compared to the wild type mice (P<0.0001), but died by 4 weeks. After allopurinol (3ug/g) intervention, they all survived > 8 weeks. The serum uric acid was 612.55±146.98μmol/L in the 8-week-old allopurinol-rescued Uox mice, which manifested multiple complications including severe renal insufficiency, hypertension, left ventricular remodeling and systolic dysfunction, aortic endothelial dysfunction, hepatic steatosis and elevated liver enzymes, as well as hyperglycemia and hypercholesteremia. The present Uox mice developed spontaneous hyperuricemia complicated with urate nephropathy, cardiovascular disease and cardiometabolic disorders, and may provide a novel tool to study hyperuricemia associated early-onset cardiovascular disorders in human.
PubMed: 38856882
DOI: 10.1007/s12265-024-10526-6 -
Pediatric Nephrology (Berlin, Germany) Jun 2024Tumor lysis syndrome (TLS) is a life-threatening metabolic disorder caused by massive tumor lysis. Allopurinol, a xanthine oxidase inhibitor, is initiated during...
Tumor lysis syndrome (TLS) is a life-threatening metabolic disorder caused by massive tumor lysis. Allopurinol, a xanthine oxidase inhibitor, is initiated during chemotherapy to prevent hyperuricemia and subsequent acute kidney injury (AKI). We report two cases of xanthine nephrolithiasis during TLS in newly diagnosed hematologic malignancy patients receiving prophylactic allopurinol. Allopurinol use likely promoted xanthine crystallization, stone formation, and AKI.
PubMed: 38842722
DOI: 10.1007/s00467-024-06413-6 -
Fitoterapia Jun 2024Coptis teeta Wall., an endangered but valuable medicinal species having various folklore uses in Indian and Chinese Traditional system of medicine. Its distribution is...
Coptis teeta Wall., an endangered but valuable medicinal species having various folklore uses in Indian and Chinese Traditional system of medicine. Its distribution is restricted to India, China and Tibet. In India, C. teeta is traditionally used in joint disorders, urinary infections and inflammatory diseases, however the scientific validation is missing. Thus, the present study aims to validate the anti-lithiatic and anti-gout activity of C. teeta rhizome extract (CTME) through in-vitro biological assays. The metabolic fingerprinting of CTME through reverse phase-high performance liquid chromatography-photodiode array (RP-HPLC-PDA) showed the presence of five benzyl-isoquinoline alkaloids, namely berberine (2.59%), coptisine (0.746%) jatrorrhizine (0.133%), palmatine (0.03%) and tetrahydropalmatine (0.003%). The anti-gout potency analysed via in-vitro xanthine oxidase (XOD) inhibition assay, followed by HPTLC (High performance thin layer chromatography) mediated bio-autographic inhibition of XOD signifies that CTME exhibit strong inhibition of XOD (IC: 3.014 μg/ml), insignificantly different (p > 0.05) from allopurinol (IC: 2.47 μg/ml). The XOD bioautographic assay advocates that the efficacy is primarily due to berberine and coptisine alkaloids. The CTME has significant anti-lithiatic activity, and thereby limiting the progression of crystal nidus formation, mediated via inhibition of calcium oxalate crystals nucleation and aggregation. Additionally, the extract also exhibits potential effect on inhibition of oxidative stress associated inflammation, which plays crucial role in alleviating urolithiasis and gouty conditions. Validating the traditional claims of C. teeta will not only confirm its medicinal benefits for targeted pathological conditions but also enhance its industrial demand.
PubMed: 38838823
DOI: 10.1016/j.fitote.2024.106050