Metal binding by pharmaceuticals. Part 3. Copper (II) and zinc (II) interactions with isoniazid.

Formation constants for copper(II) and zinc(II) complexes of isonicotinoylhydrazine (isoniazid) and guanosine-5'-monophosphate have been measured potentiometrically at 37 degrees C, I = 150 mmol dm-3 [NaCl]. These constants have been used in computer models to assess the extent of complex formation by the drug in vivo. The simulations indicate that the predominant complexes existing in blood plasma are ternary species formed with histidinate. However, at clinical levels of isoniazid, it seems unlikely that these complexes are physiologically significant. On the other hand, ternary complex formation with nucleosides may be involved in the binding of isoniazid to viral RNA.