Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment

Abstract

The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m², including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment.

Febuxostat in patients with hyperuricemia and severe chronic kidney disease

“…Thus, renal function should be regularly monitored during drug treatment for ensuring safety. No serious adverse reaction occurred during the study, which is similar to the finding in previous study using febuxostat in severe CKD patients (Sircar et al, 2015;Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014;Sakai et al, 2014). The results indicate the safety of febuxostat use in CKD patients.…”

“…However, previous information on the efficacy and safety of febuxostat use in CKD patients above stage 3 is limited. Several studies explored the efficacy and safety of using febuxostat for treating patients undergoing advanced CKD treatment (Table 5) (Sircar et al, 2015;Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014;Sakai et al, 2014). However, because of the limited number of patients included in this study and lower dosages used, further research is required for verifying the results.…”

“…To increase the clinical use and safety of febuxostat, several recent studies focused on its efficacy and safety in patients with severe CKD. However, the number of included patients was low (Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014). The present study assessed the efficacy and safety of febuxostat in controlling hyperuricemia in patients with severe CKD.…”

“…Its metabolite, oxypurinol, may accumulate in the body of patients with insufficient renal function (GFR <50 ml/min/1.73 m 2 ) and produce toxicity; therefore, dosage adjustments are necessary during treatment. However, treatment efficacy is associated with dosage, and a decrease in the dosage may cause difficulty in achieving the treatment goal of controlling sUA levels (Hira et al, 2015).…”

Updated Eular Guidelines for the Management of Gout. Comments on Certain Items

“…У пациентов с ХБП эффективность фебук-состата превышает таковую аллопуринола в случае приме-нения последнего в низких дозах, рассчитанных исходя из клиренса креатинина [106,119].…”