RHODOTORULIC ACID - INVESTIGATION OF ITS POTENTIAL AS AN IRON-CHELATING DRUG

  • 1 January 1979
    • journal article
    • research article
    • Vol. 209  (3) , 342-348
Abstract
Although the anemia associated with .beta.-thalassemia major can be alleviated with an appropriate transfusion regimen, the resulting secondary hemochromatosis leads to fibrotic changes of vital organs, particularly the heart. Usually patients die of cardiac failure toward the end of the second decade. Presumably the fibrotic changes could be avoided if a means were available to remove excess Fe from the body. The use of rhodotorulic acid (RA) as an Fe chelating drug was suggested by experiments in hypertransfused rats in which urinary and fecal Fe excretion were significantly enhanced in response to RA. The toxicity of the drug appears to be minimal at a parenteral dose less than 250 mg/kg. An increased excretion of Zn was the only notable side effect of the drug at the doses used. When administered i.v. to humans, RA was only 16% more effective than desferrioxamine (DF). Pharmacokinetic studies showed that RA persisted in the bloodstream of dogs 6 times longer than desferrioxamine after an i.v. injection. Accordingly RA was evaluated as a potential repository drug. While animal experiments were encouraging, human subjects experienced a painful local reaction to RA administered either i.m. or s.c. as a suspension in physiological saline. Accordingly it appears that RA is best looked at as a 2nd line drug, unless a means can be found to obviate local inflammatory reactions.