Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). I. Iron chelation and metabolic studies.
作者： G. J. Kontoghiorghes , A. N. Bartlett , A. V. Hoffbrand , J. G. Goddard , L. Sheppard
DOI: 10.1111/J.1365-2141.1990.TB07887.X
关键词:
摘要: A long-term clinical trial of 1-15 months has been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in 13 transfusion-dependent iron-loaded patients. Urinary excretion was greatest patients thalassaemia major and related to number previous transfusions but not serum ferritin level. Substantial increases urinary were observed all when frequency daily dose doubled response 2 x 3 g L1 11 12 tested excreted greater than 25 mg daily, mean intake from transfusion. Serum levels have fluctuated overall remained unchanged. Pharmacological studies five indicated rapid absorption probably stomach variable plasma half life 77 +/- 35 min (X SD). Glucuronation identified as a route metabolism. Short-term intensive chelation using repeated administration resulted further by comparison single dose. In one case 325 urine following 16 (5 + g) within 24 h. Iron six transfusional who maintained on low diet before during chelation. No significant faecal doses up 4 g. The high level compliance treatment that can be achieved increase prospects for
sci-hub.se 参考文章(19)
MJ Pippard, ST Callender, CA Finch, Ferrioxamine excretion in iron-loaded man Blood. ,vol. 60, pp. 288- 294 ,(1982) , 10.1182/BLOOD.V60.2.288.288
GeorgeJ. Kontoghiorghes, Lyndon Sheppard, MaadhA. Aldouri, A.Victor Hoffbrand, 1,2-DIMETHYL-3-HYDROXYPYRID-4-ONE, AN ORALLY ACTIVE CHELATOR FOR TREATMENT OF IRON OVERLOAD The Lancet. ,vol. 329, pp. 1294- 1295 ,(1987) , 10.1016/S0140-6736(87)90545-9
George J. Kontoghiorghes, Lyndon Sheppard, Simple synthesis of the potent iron chelators 1-alkyl-3-hydroxy-2-methylpyrid-4-ones Inorganica Chimica Acta. ,vol. 136, ,(1987) , 10.1016/S0020-1693(00)85549-8
Hans H. Rennhard, The metabolism of ethyl maltol and maltol in the dog. Journal of Agricultural and Food Chemistry. ,vol. 19, pp. 152- 154 ,(1971) , 10.1021/JF60173A036
A.V. Hoffbrand, A. Gorman, M. Laulicht, M. Garidi, J. Economidou, P. Georgipoulou, M.A.M. Hussain, D.M. Flynn, Improvement in iron status and liver function in patients with transfusional iron overload with long-term subcutaneous desferrioxamine. The Lancet. ,vol. 313, pp. 947- 949 ,(1979) , 10.1016/S0140-6736(79)91721-5
A. N. Bartlett, A. V. Hoffbrand, G. J. Kontoghiorghes, Long‐term trial with the oral iron chelator 1,2‐dimethy1‐3‐hydroxypyrid‐4‐one (L1) II. CLINICAL OBSERVATIONS British Journal of Haematology. ,vol. 76, pp. 301- 304 ,(1990) , 10.1111/J.1365-2141.1990.TB07888.X
George J. Kontoghiorghes, Dose response studies using desferrioxamine and orally active chelators in a mouse model Scandinavian Journal of Haematology. ,vol. 37, pp. 63- 70 ,(2009) , 10.1111/J.1600-0609.1986.TB01773.X
George J. Kontoghiorghes, A. Victor Hoffbrand, Orally active α‐ketohydroxy pyridine iron chelators intended for clinical use: in vivo studies in rabbits British Journal of Haematology. ,vol. 62, pp. 607- 613 ,(1986) , 10.1111/J.1365-2141.1986.TB04082.X
M.B. Agarwal, Chandra Viswanathan, J. Ramanathan, DavidE. Massil, Samir Shah, S.S. Gupte, Deepa Vasandani, R.R. Puniyani, Oral iron chelation with L1. The Lancet. ,vol. 335, pp. 601- ,(1990) , 10.1016/0140-6736(90)90380-N
G. Vreugdenhil, A.J.G. Swaak, G.J. Kontoghiorghes, H.G. Van Eijk, EFFICACY AND SAFETY OF ORAL IRON CHELATOR L1 IN ANAEMIC RHEUMATOID ARTHRITIS PATIENTS The Lancet. ,vol. 334, pp. 1398- 1399 ,(1989) , 10.1016/S0140-6736(89)92011-4