The interaction of orally administered iron with levodopa and methyldopa therapy

Author:

Greene R J1,Hall A D1,Hider R C1

Affiliation:

1. Department of Pharmacy, King's College, Manresa Road, London, UK

Abstract

Abstract The ability of methyldopa and levodopa to interact with both ferrous and ferric iron under a variety of conditions likely to be encountered physiologically has been examined. Spectrophotometric studies of ferrous sulphate in the presence of methyldopa indicate that no complexation occurs below pH 2, whilst between pH 4–9, a variety of iron-methyldopa complexes is formed. The formation of these complexes is fast at high pH (pH 9: t 1/2 < 5 s), whilst the rate slows as the pH is lowered (pH 4: t 1/2 > 30 min). These complexes are characteristic of iron-catecholate species, indicating that in the presence of methyldopa (and levodopa) ferrous iron undergoes autoxidation to the ferric form. The tight binding of ferric iron to methyldopa is predicted to alter the biodistribution characteristics of the complex with respect to the unchelated components. Furthermore, under the acid conditions of the stomach, redox cycling can occur. This will result in both catechol oxidation and production of the toxic hydroxyl radical. The findings suggest that care should be exercised when simultaneous administration of either methyldopa or levodopa with ferrous sulphate is indicated.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference9 articles.

1. Alteration of methyldopa absorption, metabolism, and blood pressure control caused by ferrous sulphate and ferrous gluconate;Campbell;Clin. Pharmacol. Ther.,1988

2. Ferrous sulphate reduces levodopa bioavailability: chelation as a possible mechanism;Campbell;Ibid.,1989

3. Model compounds for microbial iron-transport compounds Part 1. Solution chemistry and Mossbauer study of iron (II) and iron (III) complexes from phenolic and catecholic systems;Hider,1981

4. Implications of two different types of diffusion for biological membranes;Lieb;Nature New Biol.,1971

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