Influence of hemodialysis on pramipexole pharmacokinetics: Lessons from two cases and literature review

Background: Restless legs syndrome (RLS) is not a rare condition in patients on long-term dialysis. Pramipexole is a small molecule used in the treatment of idiopathic and uremic RLS. Although some information concerning the efficacy and safety of pramipexole in uremic patients is available, data concerning the pharmacokinetics of pramipexole in hemodialysis (HD) are lacking. Following the occurrence of accidental pramipexole intoxication in a chronic HD patient, we were concerned about the efficacy of HD in removing pramipexole. Our aim was thus to assess plasma pramipexole concentrations and pramipexole clearance in a stable chronic HD patient without any residual kidney function. Materials and methods: Our patient was a 63-year-old man on chronic HD for 5 years who had been treated uneventfully with oral pramipexole for uremic RLS since then. During a routine 4-hour high-flux HD session, blood, ultrafiltrate, and dialysate samples were collected every hour to determine pramipexole concentrations over time. Results: Pramipexole blood concentrations ranged from 12.1 to 23.9 µg/L. Pramipexole reduction ratio was 32.5%. Mean dialytic clearance of pramipexole was 76.8 mL/min. Postdialysis rebound was 5.6%. Conclusion: In the absence of any side effect, pramipexole blood concentrations at steady state were 2- to 4-fold higher than those observed in subjects with normal kidney function. Like other drugs with a high volume of distribution, pramipexole was poorly removed by HD. Therefore, HD is not recommended as a treatment option for pramipexole intoxication in patients with a glomerular filtration rate superior to 30 mL/min/1.73m².