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 β-thalassemia

Objective: To examine the effect of frequency of oral administration of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on urinary iron excretion. Hypothesis: Sustained serum concentrations of L1 will cause more iron dictation than the same daily dose given in larger but less frequent amounts. Patients and methods: Ten patients with thalassemia with a mean age of 20.9 ± 4.7 years (range, 13 to 27 years), who were receiving regular treatment with 75 to 100 mg/kg/day oral L1, received 75 mg/kg/day L1 orally in equally divided doses: every 6 hours for 3 days and every 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 schedules. Serial blood samples were collected from six patients over a 6-hour 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 μg/L) were similar during the every-6-hour and every-12-hour L1 administrations, respectively. There was significantly more urinary iron excretion when L1 was administered every 6 hours (0.59 ± 0.29 mg/kg/day) versus every 12 hours (0.40 ± 0.26 mg/kg/day; p = 0.0129). Calculated 24-hour area under the plasma concentration-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) experiments. Conclusions: These data suggest that the sustained presence of L1 in the blood results in greater chelation of iron than that observed with larger, less frequent doses.