URINARY IRON EXCRETION DEPENDS ON THE MODE OF ADMINISTRATION OF THE ORAL IRON CHELATOR 1,2-DIMETHYL-3-HYDROXYPYRID-4-ONE IN PATIENTS WITH HOMOZYGOUS BETA-THALASSEMIA

Objective: To examine the effect of frequency of oral administration o f 1,2-dimethyl-3-hydroxypyrid-4one (L1) on urinary iron excretion. Hyp othesis: Sustained serum concentrations of L1 will cause more iron che lation than the same daily dose given in larger but less frequent amou nts. Patients and methods: Ten patients with thalassemia with a mean a ge of 20.9 +/- 4.7 years (range, 13 to 27 years), who were receiving r egular treatment with 75 to 100 mg/kg/day oral L1, received 75 mg/kg/d ay L1 orally in equally divided doses: every 6 hours for 3 days and ev ery 12 hours for 3 days. The two study periods occurred 1 month apart immediately after the monthly blood transfusions. Urine was collected for two consecutive 24-hour periods during each of the different sched ules. Serial blood samples were collected from six patients over a 6-h our period and analyzed for total L1 and the L1 glucuronide metabolite concentrations. Results: The patient's mean hemoglobin levels (138.8 +/- 12.5 and 139.0 +/- 11.6 gm/L) and ferritin levels (2856.4 +/- 2207 .8 and 2890.0 +/- 2264.4 mu g/L) were similar during the every-6-hour and every-12-hour L1 administrations, respectively. There was signific antly more urinary iron excretion when L1 was administered every 6 hou rs (0.59 +/- 0.29 mg/kg/day) versus every 12 hours (0.40 +/- 0.26 mg/k g/day; p = 0.0129). Calculated 24-hour area under the plasma concentra tion-time curve of L1 was similar during the every-6-hour (7023.9 +/- 2637.8 mg min/L) and every-12-hour (7050.1 +/- 1668.8 mg.min/L) experi ments. Conclusions: These data suggest that the sustained presence of L1 in the blood results in greater chelation of iron than that observe d with larger, less frequent doses.