Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism.
This study examined the effect of ferrous sulfate, a widely used iron treatment, on levodopa bioavailability in normal subjects. A 250 mg tablet of levodopa was taken with and without a 325 mg tablet of ferrous sulfate by eight normal subjects in a randomized crossover trial. When levodopa was taken with ferrous sulfate there was a 55% decrease in peak levodopa levels (3.6 +/- 2.6 vs 1.6 +/- 0.82 nmol/ml; p less than 0.05) and a 51% decrease in AUC (257 +/- 133 vs 125 +/- 51 nmol.min/ml; p less than 0.01). Persons with the highest peak levodopa levels and AUC after levodopa alone had the greatest reduction in peak levodopa levels and AUC after levodopa ingestion with ferrous sulfate. Iron in its ferrous state is oxidized rapidly to the ferric state in the presence of levodopa at pHs found in the small intestine. In the ferric state, iron binds very strongly to levodopa. Chelation of iron by levodopa is the likely mechanism for this drug interaction. The clinical significance of this interaction is yet to be established.
Campbell
N R
NR
Discipline of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Hasinoff
B
B
D000328:Adult; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D005296:Ferrous Compounds / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007502:Iron Chelating Agents / Q000378:metabolism*; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010084:Oxidation-Reduction; D011897:Random Allocation
D005296:Ferrous Compounds; D007502:Iron Chelating Agents; C020748:ferrous sulfate; D007980:Levodopa