Efficacy and (Pharmaco)Kinetics of One Single Dose of Rasburicase in Patients with Chronic Kidney Disease

Abstract

Aims: Hyperuricemia is a risk factor associated with cardiovascular and renal disease. Recently, rasburicase, a recombinant urate oxidase, has been developed for the treatment of hyperuricemia in patients with primarily hematological malignancies. We studied the pharmacokinetics and metabolism of rasburicase in the treatment of chronic asymptomatic hyperuricemia in chronic kidney disease (CKD) patients. Materials and Methods: We studied 9 CKD patients with hyperuricemia, whose mean serum acid concentration was 10.2 (range 8.3–15.8) mg/dl. No study subject was taking allopurinol (3/9 are allopurinol intolerant). Patients were treated with rasburicase (0.2 mg/kg/day) in single dose by intravenous infusion over a 30-min period. Serum samples were collected after 1, 4, 8, 24, 48 and 72 h, after 1 week, and after 1 month. To evaluate the efficacy of rasburicase, plasma and urinary concentrations of uric acid were determined by the standard method; the plasma activity of rasburicase was determined using a new assay developed by our laboratory (chromatography-mass method, a colorimetric 96-well microtiter plate assay). Results: All the treated patients experienced a rapid reduction in their plasma uric acid concentration. Data showed an undetectable value within 1 h of treatment. The rasburicase effect ended after 50 h, with a slow increase in the plasma level of uric acid. Conclusion: A single dose of rasburicase is highly effective and well tolerated in the treatment of hyperuricemia in selected CKD patients.

Onco-Nephrology

“…An expert panel convened in 2010, sponsored by the manufacturer of rasburicase (SanofiAventis), recommended the prophylactic use of rasburicase in adults with a high-risk malignancy, with other patients receiving rasburicase after chemotherapy in the setting of elevated uric acid levels (51). Several cohort studies have demonstrated persistently suppressed serum uric acid concentrations with one-time dosing; a dose of 0.15 mg/kg seems to be a clinically reasonable and cost-effective approach (62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74). Repeat dosing may be needed if uric acid remains at or increases above 8.0 mg/dl after the initial dose (75).…”

Uricases as Therapeutic Agents to Treat Refractory Gout: Current States and Future Directions

“…Raburicase and pegloticase are approved uricase formulations for treating hyperuricemia. Raburicase is a recombinant fungal uricase without structural modification and is used for short-term treatment of TLS [Bessmertny et al, 2005;Vogt, 2005;Richette and Bardin, 2006;Sestigiani et al, 2008]. Pegloticase is a chimera of porcine and baboon liver uricases and is designed for the continuous treatment of refractory gout [Sundy et al, 2007;Fels and Sundy, 2008;Sherman et al, 2008;Yue et al, 2008;Chohan and Becker, 2009;Terkeltaub, 2010;Schlesinger et al, 2011].…”

“…) [Chohan and Becker, ; Richette and Bardin, ] but it is not widely used due to associated kidney and liver toxicity. Uricase is a unique anti‐hyperuricemia drug acting on urate [Bessmertny et al., ; Vogt, ; Richette and Bardin, , ; Fels and Sundy, ; Sestigiani et al., ; Sherman et al., ; Chohan and Becker, ; Mughal et al., ; Terkeltaub, ; Schlesinger et al., ], catalyzing the oxidation of urate into hydrogen peroxide and 5‐hydroxyisourate (HIU) [Ramazzina et al., ]. HIU spontaneously decomposes to allantoin and carbon dioxide.…”

“…Gout, with a prevalence of about 1%, is characterized by the sustained elevation of plasma urate levels [Davidson et al, 2004;Kang and Nakagawa, 2005;Chohan and Becker, 2009;Richette and Bardin, 2010]. CKD is usually associated with hyperuricemia and has a prevalence of about 5% [Kang and Nakagawa, 2005;Sestigiani et al, 2008;Feig, 2009].…”