title: 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.
abstract: OBJECTIVE
  To examine the effect of frequency of oral administration of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on urinary iron excretion.
  
  
  OBJECTIVE
  Sustained serum concentrations of L1 will cause more iron chelation than the same daily dose given in larger but less frequent amounts.
  
  
  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 micrograms/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.
authors.affiliation: Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: F F
authors.initials: FF
authors.lastname: Fassos
authors.forename: J
authors.initials: J
authors.lastname: Klein
authors.forename: D
authors.initials: D
authors.lastname: Fernandes
authors.forename: D
authors.initials: D
authors.lastname: Matsui
authors.forename: N F
authors.initials: NF
authors.lastname: Olivieri
authors.forename: G
authors.initials: G
authors.lastname: Koren
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000077543:Deferiprone; D004334:Drug Administration Schedule; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007501:Iron / Q000652:urine*; D007502:Iron Chelating Agents / Q000378:metabolism*; D011728:Pyridones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron