Metal binding by pharmaceuticals. Part 1. Copper(II) and zinc(II) interactions following ethambutol administration.
Formation constants for copper(II) and zinc(II) complexes of dextro-2,2'-(ethylenediimino)-di-1-butanol (ethambutol) and its metabolic oxidation product, 2,2'-(ethylenediimino)-dibutyric acid (EDBA) have been measured potentiometrically at 37 degrees C, I = 0.15 mol dm-3 [NaCl]. The constants are used in computer models to assess the extent of the formation of these complexes in vivo. These simulations indicate that whereas ethambutol forms metal complexes only to a limited extent in vivo, EDBA competes effectively under physiological conditions for copper(II) and zinc(II). This study suggests that zinc(II) binding by EDBA may account for a number of side effects of ethambutol treatment.
D002614:Chelating Agents / Q000378:metabolism; D003201:Computers; D003300:Copper / Q000097:blood / Q000378:metabolism*; D004977:Ethambutol / Q000009:adverse effects / Q000378:metabolism*; D005029:Ethylenediamines / Q000378:metabolism; D006801:Humans; D011199:Potentiometry; D015032:Zinc / Q000097:blood / Q000378:metabolism*
D002614:Chelating Agents; D005029:Ethylenediamines; C030779:EDBA; D003300:Copper; D004977:Ethambutol; D015032:Zinc