Introduction. Allopurinol, a urate-lowering therapy used to manage gout, is commonly prescribed in patients receiving haemodialysis (HD). Urate is effectively removed by HD raising the question of whether allopurinol is needed to achieve the serum urate (SU) target of < 0.36 mmol/L.
Aims. To simulate SU concentration changes for a typical gout patient with CKD stage 5 taking allopurinol 100 mg daily with and without dialysis and after allopurinol dose reduction and deprescribing.
Methods. A semi-mechanistic PKPD model was built using a PK model for oxypurinol (Hishe et al, 2023) and a PD model for uric acid (Hill-McManus et al, 2018). An additional compartment was added to capture intestinal urate clearance and dialysis was added as a flag (on/off). A single subject simulation of SU concentrations was conducted for a typical gout patient weighing 85 kg with CKD stage 5. Nine pre-dialysis SU concentrations were tested in 0.05 increments (0.33-0.69 mmol/L). SU was simulated for allopurinol 100 mg/day over 4 months without HD. At 4 months, HD thrice weekly over 4 h was initiated. At month 5, the allopurinol dose was reduced to 50 mg/day, and at month 6 allopurinol was discontinued. The model was coded in R package ‘mrgsolve’ (R 4.5.1). Average steady-state weekly SU concentrations (SUss,avg,) were reported.
Results. After the initiation of HD, the SUss,avg was < 0.36 mmol/L for allopurinol 100 and 50 mg daily and after allopurinol deprescribing. (Fig. Pre-HD SU 0.33, 0.56 and 0.69 mmol/L depicted).
Discussion. Our indicative results suggest that allopurinol deprescribing may be feasible in some patients with gout on HD without a loss of efficacy. These findings support prospective allopurinol deprescribing studies for patients receiving HD.
References.
- Hill‑McManus D et al. (2018). Br J Clin Pharmacol, 84, 142–152
- Hishe HZ et al. (2023). Clin Transl Sci, 16, 422–428.