Pharmacokinetic interaction of tetracycline with non-steroidal anti-inflammatory drugs via organic anion transporters in rats

The present study aims to investigate the pharmacokinetic interaction between non-steroidal anti-inflammatory drugs and tetracycline in rats. Pharmacokinetic parameters were determined following an intravenous administration of tetracycline (5 mg kg−1) to rats in the presence and absence of naproxen or diclofenac (20 mg kg−1). Compared to the control (given tetracycline alone), pretreatment with naproxen or diclofenac 30 min prior to tetracycline administration significantly altered the pharmacokinetics of tetracycline. Renal clearance of tetracycline was reduced by approximately three-fold in the presence of naproxen or diclofenac. Consequently, the systemic exposures (AUC) of tetracycline in the rats pretreated with naproxen or diclofenac were significantly (p < 0.05) higher than those from the control group given tetracycline alone. Furthermore, mean terminal plasma half-life of tetracycline was enhanced by two- to five-folds under the pretreatment with naproxen or diclofenac. Those results suggest that NSAIDs such as naproxen and diclofenac are effective to alter the renal elimination and pharmacokinetic profiles of tetracycline. Therefore, concomitant use of naproxen or diclofenac with tetracycline may require close monitoring for clinical consequence of potential drug interaction.