Metal ion-tetracycline interactions in biological fluids. Part 5. Formation of zinc complexes with tetracycline and some of its derivatives and assessment of their biological significance.

A series of studies was previously devoted to the dependence of the bioavailability of various tetracyclines on their coordination with calcium and magnesium ions. Several clinical investigations have also shown zinc to interfere with the gastrointestinal absorption of the drug in humans. On the other hand, the administration of tetracycline to rats was reported to result in the increase of the elimination rate of zinc, which could originate in zinc-tetracycline interactions in blood plasma. Formation constants for zinc complexes with tetracycline, oxytetracycline, doxycycline, minocycline, chlortetracycline and demethylchlortetracycline were thus determined at 37 degrees C in NaCl 0.15 mol. dm-3 aqueous medium. Computer simulations were then carried out to investigate the drug influence on the distribution of the low-molecular-weight fraction of zinc in human blood plasma. Zinc-tetracycline interactions in the gastrointestinal fluid were also simulated, using clinical data relative to fasting subjects as taken from the literature. No significant effect can be expected from tetracyclines on the distribution of zinc in plasma at the usual therapeutic levels. However, zinc-tetracycline interactions have been found to be determining factors for the bioavailabilities of the metal as well as of the antibiotic in the gastrointestinal fluid.