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Pharmacokinetics of the oral iron chelator deferiprone (L 1 ) in patients with iron overload
Author(s) -
ALRefaie F. N.,
Sheppard L. N.,
Nortey P.,
Wonke B.,
Hoffbrand A. V.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb03318.x
Subject(s) - deferiprone , pharmacokinetics , deferasirox , medicine , deferoxamine , pharmacology , thalassemia
Summary. Single oral dose pharmacokinetics of the iron chelator deferiprone (L 1 ) were studied in 24 patients with chronic iron overload and correlated with 24h urinary iron excretion (UIE) and creatinine clearance. Absorption of L 1 was rapid with a t 1/2 of 22·2 pL 17·7 (mean pL SD) min. The elimination half‐life (el t 1/2 ) of the drug was 91·1 pL 33·1 min and of its metabolite, L 1 ‐glucuronide (L 1 G) 147·7pL 52·0 min. Creatinine clearance of the patients correlated significantly with the elimination t 1/2 of L 1 G ( r = ‐0·79, P = 0·002). There was also a significant correlation between 24 h UIE in the 14 patients studied and L 1 versus time area under the curve (AUC) ( P = 0·007). The total amount of L 1 recovered in urine in 24 h comprised 77·9 pL 13·3% of the L 1 dose. L 1 efficiency (the 24 h UIE divided by the amount of iron the oral dose of L 1 is capable of binding) in the 14 patients was 3·8 pL 1·9%. These data show for the first time that the urinary elimination of L 1 G is influenced by the renal function of the patient. Although no significant accumulation of L 1 and L 1 G will occur in most of the patients if L 1 is given more than once daily, in some patients with impaired renal function, L 1 G may accumulate.