Kontoghiorghes G J, Goddard J G, Bartlett A N, Sheppard L
Department of Haematology, Royal Free Hospital School of Medicine, London, England.
Clin Pharmacol Ther. 1990 Sep;48(3):255-61. doi: 10.1038/clpt.1990.147.
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 beta-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.
已对口服铁螯合剂1,2 - 二甲基 - 3 - 羟基吡啶 - 4 - 酮（L1）进行了药代动力学研究。对一名正常志愿者和七名摄入3克剂量L1的输血性铁过载患者的血清进行HPLC分析显示，L1很可能从胃部吸收，并以0.7至32分钟的半衰期转移至血液中。L1在给药后12至120分钟达到血清最大浓度，在前5至6小时内消除85%至90%，半衰期为47至134分钟。在血清和尿液中鉴定出了L1及其葡萄糖醛酸代谢物，但粪便中未检出。在大多数情况下，使用β - 葡萄糖醛酸酶水解24小时尿液样本可使给药剂量几乎完全回收。尿铁排泄与铁负荷成正比，但与L1的血清或尿液浓度无关。因此，通过至少每6小时重复给予2至3克剂量，可提高L1的治疗效果。
