Aim: Febuxostat is initiated in chronic kidney disease (CKD) patients to lower uric acid but without any renal dosing scheme. This study aimed to determine a formula that predicts the effective dose of febuxostat in patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min and asymptomatic hyperuricemia.
Materials And Methods: This is a retrospective analysis of 100 CKD patients treated with febuxostat for asymptomatic hyperuricemia in two private Lebanese clinics. Patients with gout were excluded. Collected variables were age, sex, weight, serum creatinine, serum uric acid (sUA) before and after febuxostat, dose of febuxostat used, and diuretic use. Multiple regression analysis was used to derive a formula predicting the dose of febuxostat based on eGFR (2009 Chronic Kidney Disease Epidemiology Collaboration equation), baseline sUA, and sUA reduction ratio. A prospective cohort of 24 patients was then used to validate the derived model.
Results: 100 patients were included with a median age of 71.5 years (interquartile range (IQR), 64.2 - 79.0); 69% were men. Median baseline sUA was 9.1 mg/dL (IQR, 8.4 - 10.1). Mean eGFR was 31.80 ± 12.96 mL/min/1.73m. Of the included patients, 18% had CKD stage 3a, 36% had CKD stage 3b, 38% had CKD stage 4, and 8% had non-dialysis CKD stage 5. A formula was computed to predict febuxostat dosing. Variables that were predictive of febuxostat dose and used in the final equation were eGFR, diuretic use, baseline sUA, and sUA reduction ratio. The validation cohort showed no significant difference between the expected sUA and the measured one (p = 0.16).
Conclusion: With this new formula, physicians can initiate febuxostat in CKD patients at an effective dose for any desired sUA reduction ratio.
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http://dx.doi.org/10.5414/CN109867 | DOI Listing |
Cureus
October 2024
Hematology and Medical Oncology, Northwell Health, New Hyde Park, USA.
Rasburicase is a recombinant form of urate oxidase, a medication used to treat hyperuricemia by metabolizing uric acid into an inactive and more soluble metabolite, allantoin. An oxidizing agent, hydrogen peroxide, is produced during the conversion of uric acid to allantoin. We present here a case of hemolytic anemia secondary to rasburicase treatment which was later confirmed to have glucose-6-phosphate dehydrogenase deficiency (G6PDD).
View Article and Find Full Text PDFPharmacol Res Perspect
December 2024
Translational Science Research Department, Teijin Institute for Bio-medical Research, Teijin Pharma Limited, Tokyo, Japan.
The study objective was to validate febuxostat dosage and administration in pediatric patients with hyperuricemia including gout, using an integrated population pharmacokinetic (PopPK) analysis in the Japanese population. Integrated PopPK analysis of febuxostat used a nonlinear mixed-effects modeling (NONMEM) program on plasma febuxostat concentration data for 2611 samples from Japanese pediatric patients with hyperuricemia including gout (n = 29) and from adult subjects who are healthy or have renal dysfunction (n = 113). We described febuxostat pharmacokinetics using an integrated PopPK model applicable both to pediatric patients and to the adult population.
View Article and Find Full Text PDFThe treatment of gout includes anti-inflammatory therapy and prophylaxis of flare-ups on the one hand and measures for long-term uric acid reduction on the other. Acute arthritis urica is best relieved by intra-articular steroids; systemic steroids, NSAIDs and, in exceptional cases, colchicine are also suitable. For the prophylaxis of relapses, long-term use of colchicine, NSAIDs or low-dose steroids is an option.
View Article and Find Full Text PDFFood Chem Toxicol
December 2024
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt. Electronic address:
Experimental models of liver injury have been established utilizing thioacetamide (TAA), a classic liver toxic chemical that causes organ damage via oxidative stress and inflammatory induction. This study examined the impact of Febuxostat (a xanthine oxidase inhibitor; Febu, 10-15 mg/kg, orally) against TAA (500 mg/kg, i.p.
View Article and Find Full Text PDFEur J Med Chem
December 2024
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, 110031, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taiwan. Electronic address:
Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition.
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