STUDIES OF ALUMINUM MOBILIZATION IN RECTAL 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 c ollected before haemodialysis at 1 h and for some patients at longer i ntervals. Plasma aluminium levels before treatment ranged from 12 to 2 64 mu g/l. A mean increase of 90% was observed within the first hour o f oral administration of 6 patients who received a dose of L1 of 40-60 mg/kg. Plasma aluminium levels then progressively decreased after thi s period. Three patients with plasma aluminium of 30-66 mu g/l who rec eived 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 resulte d in an over 30-fold increase of aluminium concentration in the dialys ate of a continuous ambulatory peritoneal dialysis patient and of over 3 times the iron concentration in the dialysate of an iron loaded hae modialysis 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 6.5h of the L1 administration. No toxic side effects were observed in any of t he 11 patients who received oral L1. These are the first clinical tria ls of an oral chelator in renal dialysis patients which suggest that o ral L1 and possibly other a-ketohydroxypyridine chelators may have a u se in the treatment of patients with aluminium overload.