Inhibition of tetracycline absorption by zinc

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

“…The gastrointestinal absorption of tetracycline and its derivatives is known to be impaired by the simultaneous ingestion of food and antacids containing various metal ions [30,31]. Tetracyclines have their optimum solubility at low pH values and the effects of the antacids may logically be attributed to the reduced dissolution correlated to the raising of the gastric pH [29].…”

“…Tetracyclines have their optimum solubility at low pH values and the effects of the antacids may logically be attributed to the reduced dissolution correlated to the raising of the gastric pH [29]. Besides, complexation of the ,drug with metal ions was also shown to be directly responsible for its reduced absorption [31,[48][49][50], the more so as (i) the effects were observed to be dependent on the nature of the anion of the metal salt [30,40,51], (ii) the absorption of the metal itself was proved to be simultaneously affected [34,48].…”

“…Concerning the interactions of zinc with tetracycline and its derivatives, ANDERSSON et al [30] observed that the oral administration of 200 mg Of zinc sulphate (45 mg Zn 1+) together with 500 mg of tetracycline mixed in 200 ml of water reduced the serum concentration of antibiotic by more than 50%. As was pointed out in that study, the fact that zinc citrate was shown to reduce the drug serum concentration to a lesser extent than zinc sulphate tends to accredit the hypothesis that a competition exists between citrate and tetracycline for zinc in the gastrointestinal fluid.…”

“…Many reports are available in the literature which refer to the high affinity of these substances for transition metal ions [22][23][24][25][26][27][28]. In this respect, several clinical investigations were devoted to the potential influence of zinc on the gastrointestinal absorption of tetracyclines [29][30][31]. Zinc was shown to exert an important antagonism against the absorption of tetracycline itself [29][30][31], but this effect proved less signifi-cant for doxycycline [31].…”

“…In this respect, several clinical investigations were devoted to the potential influence of zinc on the gastrointestinal absorption of tetracyclines [29][30][31]. Zinc was shown to exert an important antagonism against the absorption of tetracycline itself [29][30][31], but this effect proved less signifi-cant for doxycycline [31]. Tetracycline absorption being a passive diffusion phenomenon [32], the possible formation of electrically charged complexes of zinc may indeed reduce the proportion of the lipophilic forms of the antibiotic.…”