title: Altered pharmacokinetics of zalcitabine by concurrent use of NSAIDs in rats.
abstract: OBJECTIVE
  To investigate the pharmacokinetic interactions between zalcitabine and nonsteroidal anti-inflammatory drugs (NSAIDs) in rats.
  
  
  METHODS
  Zalcitabine was administered to rats via an iv injection (20 mg/kg) in the presence or absence of ketoprofen or naproxen (20 mg/kg), and the pharmacokinetic parameters were determined by using non-compartmental analysis.
  
  
  RESULTS
  Compared with the control (zalcitabine alone), pretreatment with ketoprofen or naproxen 30 min prior to intravenous administration of zalcitabine significantly altered the pharmacokinetic profiles of zalcitabine in rats. Renal clearance of zalcitabine was reduced by approximately 3-4-fold in the presence of ketoprofen or naproxen. Consequently, systemic exposure (AUC) to zalcitabine in the rats pretreated with ketoprofen or naproxen was significantly greater than that for the control group given zalcitabine alone. The terminal plasma half-life of zalcitabine was also prolonged by 4-5-fold in the presence of ketoprofen or naproxen.
  
  
  CONCLUSIONS
  The NSAIDs ketoprofen and naproxen effectively altered the pharmacokinetics of zalcitabine. Therefore, concomitant use of ketoprofen or naproxen in patients being treated with zalcitabine may necessitate close monitoring for potential drug interactions.
authors.affiliation: College of Pharmacy, Chosun University, Gwangju, Korea. hkhan@chosun.ac.kr
authors.forename: Yo-han
authors.initials: YH
authors.lastname: Oh
authors.forename: Hyo-kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000652:urine; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019540:Area Under Curve; D004347:Drug Interactions; D007660:Ketoprofen / Q000494:pharmacology*; D008297:Male; D009288:Naproxen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016047:Zalcitabine / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D019380:Anti-HIV Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D016047:Zalcitabine; D007660:Ketoprofen