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 correlated with 24 h urinary iron excretion (UIE) and creatinine clearance. Absorption 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 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 +/- 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 +/- 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.