The influence of indomethacin co-administration on ofloxacin levels in plasma and cerebrospinal fluid in rats

• Published in: International journal of antimicrobial agents 2004-04, Vol.23 (4), p.371-376
• Main Authors: Dontas, Ismene, Sokolis, Dimitrios P, Giamarellos-Bourboulis, Evangelos J, Tzonou, Anastasia, Giamarellou, Helen, Karayannacos, Panayotis E
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; Anti-Infective Agents - blood; Anti-Infective Agents - cerebrospinal fluid; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Central Nervous System; Central nervous system adverse effects; Drug Therapy, Combination; Female; Indomethacin; Indomethacin - administration & dosage; Medical sciences; Ofloxacin; Ofloxacin - administration & dosage; Ofloxacin - adverse effects; Ofloxacin - blood; Ofloxacin - cerebrospinal fluid; Pharmacokinetics; Pharmacology. Drug treatments; Rats; Rats, Wistar
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2003.09.016

The possible increase of ofloxacin levels in serum and cerebrospinal fluid (CSF) by concomitant indomethacin administration was investigated in 120 healthy adult rats. The animals were administered intramuscular doses of ofloxacin 30 mg/kg alone (Group A, n=60) or with indomethacin 2 mg/kg (Group B, n=60). Blood and CSF samples were obtained from both groups at 30, 45, 60 and 90 min post-administration. Concentrations of ofloxacin were estimated using a microbiological assay. Co-administration of indomethacin did not affect plasma levels of ofloxacin significantly; however, higher levels were found in all CSF samples after co-administration with indomethacin, particularly after 90 min with 0.59 μg/ml versus zero median values when only ofloxacin was administered ( P=0.05). No central nervous system adverse effects were observed clinically. No correlation between levels of ofloxacin in plasma and CSF could be established either in rats administered only ofloxacin or in rats administered both drugs. The presented pharmacokinetic findings revealed that co-administration of ofloxacin and indomethacin may result in protracted quinolone levels in the CSF. However, the absence of significant correlation between concentrations of ofloxacin in plasma and CSF upon co-administration of indomethacin, as well as of central nervous system adverse effects, make the probability of an epileptogenic interaction between them unlikely. These results merit further clinical evaluation.