Effect of aspirin on the disposition of tetracycline in sheep

ABSTRACT

Aspirin has been shown to increase the rate of urinary excretion of tetracycline in humans. To understand the mechanisms involved in this drug interaction, the effect of aspirin on the kinetics of tetracycline was investigated in sheep. Tetracycline was administered intravenously in six mixed-breed sheep at various stages first, tetracycline alone; second, immediately after intravenous injection of salicylic acid and third, three hours following oral administration of tetracycline. Blood samples were collected during 6 hours after administration of tetracycline followed by the separation of sera. Tetracycline content of each sample was assayed using fluorescence spectroscopy. The concentration of tetracycline in the first blood sample was higher when tetracycline was administered alone compared with those given after oral aspirin or with salicylic acid. Serum tetracycline concentration was more rapidly approached to the minimum when it was administered in conjunction with salicylic acid. In addition, the area under the curve for serum tetracycline concentration versus time [AUC] was smaller compared to when tetracycline was administered alone. In contrast, when aspirin was given orally prior to the 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. As the underlying mechanism[s] will have pharmacokinetics impact, which may be important in clinical pharmacology point of view, further in vivo and in vitro studies should be carried out to elucidate the exact nature of the interaction between these drugs