Effects of non-steroidal anti-inflammatory drugs on the pharmacokinetics and elimination of aciclovir in rats.
This study aims to investigate the effect of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on the pharmacokinetics and the renal elimination of aciclovir in rats. Pharmacokinetic parameters were determined following an intravenous administration of aciclovir (5 mg kg(-1)) to rats in the presence and absence of ketoprofen or naproxen (25 mg kg(-1)). Compared with the control (given aciclovir alone), pre-treatment with ketoprofen or naproxen 30 min before aciclovir administration significantly altered the pharmacokinetics of aciclovir. Renal clearance of aciclovir was reduced by approximately two fold in the presence of ketoprofen or naproxen. Consequently, the systemic exposure (AUC) to aciclovir in the rats pre-treated with ketoprofen or naproxen was significantly (P < 0.05) higher than that from the control group given aciclovir alone. Furthermore, the mean terminal plasma half-life of aciclovir was enhanced by 4-5 fold by pre-treatment with ketoprofen or naproxen. These results suggest that NSAIDs, such as ketoprofen and naproxen, are effective in altering the pharmacokinetics of aciclovir by inhibiting the organic anion transporter-mediated tubular secretion of aciclovir. Therefore, concomitant use of ketoprofen or naproxen with aciclovir should require close monitoring for clinical consequence of potential drug interaction.
Gwak
Hye-Sun
HS
College of Pharmacy, Ewha Woman's University, Daehyun-dong, Seoul, Korea.
Oh
Jung-Hyun
JH
Han
Hyo-Kyung
HK
D000212:Acyclovir / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000652:urine; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019540:Area Under Curve; D004357:Drug Synergism; D006207:Half-Life; D007275:Injections, Intravenous; D007660:Ketoprofen / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D009288:Naproxen / Q000494:pharmacology*; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D019380:Anti-HIV Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D027362:Organic Anion Transport Protein 1; D009288:Naproxen; D007660:Ketoprofen; D000212:Acyclovir