Studies of aluminium mobilization in renal dialysis patients using the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one.
The oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1, deferiprone, CAS 30652-11-0) has been tested in 11 renal dialysis patients, 10 for aluminium and 1 for iron mobilization. L1 was administered just after the patients were placed on the haemodialyser and blood samples were collected before haemodialysis at 1 h and for some patients at longer intervals. Plasma aluminium levels before treatment ranged from 12 to 264 micrograms/l. A mean increase of 90% was observed within the first hour of oral administration in 6 patients who received a dose of L1 of 40-60 mg/kg. Plasma aluminium levels then progressively decreased after this period. Three patients with plasma aluminium of 30-66 micrograms/l who received a dose of L1 of less than 30 mg/kg had no significant changes in their plasma aluminium. In 2 other cases administration of L1 resulted in an over 30-fold increase of aluminium concentration in the dialysate of a continuous ambulatory peritoneal dialysis patient and of over 3 times the iron concentration in the dialysate of an iron loaded haemodialysis patient. In the last patient HPLC analysis of the dialysate samples obtained from the haemodialyser has shown complete clearance of L1 within 4 h but not of its glucuronide metabolite within 6.5 h of the L1 administration. No toxic side effects were observed in any of the 11 patients who received oral L1. These are the first clinical trials of an oral chelator in renal dialysis patients which suggest that oral L1 and possibly other alpha-ketohydroxypyridine chelators may have a use in the treatment of patients with aluminium overload.
Department of Haematology, Royal Free Hospital and School of Medicine, University of London, UK.
G J
GJ
Kontoghiorghes
J
J
Barr
R A
RA
Baillod
D000328:Adult; D000368:Aged; D000535:Aluminum / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D000077543:Deferiprone; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011728:Pyridones / Q000009:adverse effects / Q000494:pharmacology*; D006435:Renal Dialysis; D013054:Spectrophotometry, Atomic
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D000535:Aluminum; D007501:Iron