Pharmacokinetic study on interaction between tetracycline and aspirin

To understand the mechanism involved in interaction between aspirin and tetracycline, six mixed breed dogs were premedicated with acetyl-promazine. Tetracycline hydrochloride was administered intravenously at various stages: first, tetracycline alone, second, immediately after intravenous injection of salicylic acid and third, three hours following oral administration of aspirin. Blood samples were collected during 6h after administration of tetracycline. The concentration of tetracycline was higher when it was administered alone compared with when it was given after oral aspirin or with salicylic acid. Serum tetracycline concentration was more rapidly approached to the minimum when it was administered in conjuction with salicylic acid. In addition, the area under the curve for serum tetracycline concentration versus time (AUC) was smaller compared to when tetracycline was adiministered alone. Furthermore, when aspirin was given Orally prior to intravenous administration of tetracycline, the rate of decline in serum tetracycline concentration was less and AUC was higher compared to when it was injected alone. An increase in the unbound form of tetracycline molecules may be involved which is possibly due to competition between tetracycline and salicylic acid or aspirin for plasma protein binding sites. As the underlying mechanism(s) will have pharmacokinetic impact, which may be important from clinical pharmacology point of view, further in vivo and in vitro studies should be carried out to elucidate the exact nature of this drug interaction.