The influence of indomethacin co-administration on ofloxacin levels in plasma and cerebrospinal fluid in rats.
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 microg/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.
Dontas
Ismene
I
Laboratory of Experimental Surgery and Surgical Research, Medical School, University of Athens, Athens, Greece. ismene@prodeco.gr
Sokolis
Dimitrios P
DP
Giamarellos-Bourboulis
Evangelos J
EJ
Tzonou
Anastasia
A
Giamarellou
Helen
H
Karayannacos
Panayotis E
PE
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000134:cerebrospinal fluid*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002490:Central Nervous System; D004359:Drug Therapy, Combination; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage*; D015242:Ofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000134:cerebrospinal fluid*; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015242:Ofloxacin; D007213:Indomethacin