Hrafnhildur Runólfsdóttir, Unnur Arna Þorsteinsdóttir, Inger María Schweitz Ágústsdóttir, Margrét Þorsteinsdóttir, Runólfur Pálsson and Viðar Örn Eðvarðsson
Introduction: The aim of this study was to determine the effects of allopurinol and febuxostat on plasma and urinary DHA levels in patients with adenine phosphoribosyltransferase (APRT) deficiency.
Methods and data: Patients in the APRT Deficiency Registry at Landspitali University Hospital with estimated glomerular filtration rate >30 ml/min/1.73 m2 were enrolled in a clinical trial. Following a 4-week washout period, patients were randomized to a daily dose of allopurinol 400 mg or febuxostat 40 mg for 28 days. The dose was subsequently elevated to 800 mg of allopurinol and 80 mg of febuxostat. A second washout period was followed by cross-over to the alternative drug. DHA was measured using UPLC-MS/MS.
Results: Seven patients completed the study. The median urinary DHA/creatinine ratio was 7.5 (4.3-14.0) ng/mmol off treatment, 2.1 (1.0-4.9) and 0.79 (0.2-2.2) on 400 and 800 mg of allopurinol, respectively, and 0.6 (0.3-1.0) and 0.6 (0.2-5.4) on 40 and 80 mg of febuxostat. The median plasma DHA concentration was 289 (216-432) ng/mL off treatment and 50 (32-95) ng/mL on 400 mg of allopurinol in 4 patients. The other 3 patients had concentrations below the level of quantification (BLQ). On allopurinol 800 mg/day, plasma DHA concentration was BLQ in all but 2 patients, and BLQ in all but 1 patient on both doses of febuxostat.
Conclusions: Urinary DHA excretion and plasma concentration was lower in patients on allopurinol 800 mg/day compared to 400 mg/day. Febuxostat was more efficacious in the prescribed doses.
