PHARMACOKINETICS OF THE ORAL IRON CHELATOR DEFERIPRONE (L(1)) IN PATIENTS WITH IRON OVERLOAD

Single oral dose pharmacokinetics of the iron chelator deferiprone (L( 1)) were studied in 24 patients with chronic iron overload and correla ted with 24 h urinary iron excretion (UIE) and creatinine clearance. A bsorption of L(1) was rapid with a t(1/2) of 22.2 +/- 17.7 (mean+/-SD) min. The elimination half-life (elt(1/2)) of the drug was 91.1 +/- 33 .1 min and of its metabolite, L(1)-glucuronide (L(1)G) 147.7 +/- 52.0 min. Creatinine clearance of the patients correlated significantly wit h the elimination t(1/2) of L(1)G (r = -0.79, P = 0.002). There was al so a significant correlation between 24 h UIE in the 14 patients studi ed and L(1) versus time area under the curve (AUC) (P = 0.007), The to tal amount of L(1) recovered in urine in 24 h comprised 77.9 +/- 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 patien ts was 3.8 +/- 1.9%. These data show for the first time that the urina ry elimination of L(1)G is influenced by the renal function of the pat ient. Although no significant accumulation of L(1) and L(1)G will occu r in most of the patients if L(1) is given more than once daily, in so me patients with impaired renal function, L(1)G may accumulate.