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Effects of renal impairment on the pharmacokinetics of orally administered deferiprone
Author(s) -
Fradette Caroline,
Pichette Vincent,
Sicard Éric,
Stilman Anne,
Jayashankar Shalini,
Tsang Yu Chung,
Spino Michael,
Tricta Fernando
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13037
Subject(s) - deferiprone , pharmacokinetics , medicine , renal function , urine , pharmacology , regimen , urology , thalassemia
Aims In light of the growing recognition of renal disease in thalassemia, it is important to understand the impact of renal impairment on the pharmacokinetics of iron chelators. This study evaluated the pharmacokinetics and safety of the iron chelator deferiprone (DFP) in subjects with renal impairment in comparison with healthy volunteers (HVs). Methods Thirty‐two subjects were categorized into four groups based on degree of renal impairment: none, mild, moderate or severe, as determined by estimated glomerular filtration rate (eGFR). All subjects received a single oral dose of 33 mg kg −1 DFP, provided serum and urine samples for pharmacokinetic assessment over 24 h and were monitored for safety. Results Renal clearance of DFP decreased as renal impairment increased. However, based on C max , AUC(0, t ) and AUC(0,∞), there were no significant group differences in systemic exposure, because less than 4% of the drug was excreted unchanged in the urine. DFP is extensively metabolized to a renally excreted, pharmacologically inactive metabolite, deferiprone 3‐ O ‐glucuronide (DFP‐G), which exhibited higher C max , AUC(0, t ), AUC(0,∞) and longer t max and t 1/2 in the renally impaired groups compared with HVs. The C max and AUCs of DFP‐G increased as eGFR decreased. Overall, 75%–95% of the dose was retrieved in urine, either as DFP or DFP‐G, regardless of severity of renal impairment. With respect to safety, DFP was well tolerated. Conclusions These data suggest that no adjustment of the DFP dosage regimen in patients with renal impairment is necessary, as there were no significant changes in the systemic exposure to the drug.