Premium
Pharmacokinetic studies in humans with the oral iron chelator 1,2‐dimethyl‐3‐hydroxypyrid‐4‐one
Author(s) -
Kontoghiorghes George J,
Goddard J Graham,
Bartlett Arudanthy N,
Sheppard Lyndon
Publication year - 1990
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1990.147
Subject(s) - urine , volunteer , pharmacokinetics , glucuronide , oral administration , pharmacology , metabolite , chemistry , clinical pharmacology , excretion , stomach , serum concentration , half life , medicine , biochemistry , biology , agronomy
Pharmacokinetic studies have been carried out with the oral iron chelator 1,2‐dimethyl‐3‐hydroxypyrid‐4‐one (L1). HPLC analysis of serum of a normal volunteer and seven transfusional iron loaded patients who ingested a 3 gm dose of L1 revealed that L1 was most probably absorbed from the stomach and was transferred to the blood with a half‐life of 0.7 to 32 minutes. L1 reached maximum concentration in the serum 12 to 120 minutes after administration with 85% to 90% elimination within the first 5 to 6 hours, with a half‐life of 47 to 134 minutes. L1 and its glucuronide metabolite were identified in serum and urine but not in feces. In most cases hydrolysis of 24‐hour urine samples with use of β‐glucuronidase resulted in almost complete recovery of the administered dose. Urinary iron excretion was proportional to the iron load but not to the serum or urine concentration of L1. The therapeutic efficiency of L1 can therefore be improved by repeated administration of 2 to 3 gm doses at least every 6 hours. Clinical Pharmacology and Therapeutics (1990) 48, 255–261; doi: 10.1038/clpt.1990.147