Increases in Serum, Brain and Cerebrospinal Fluid Levels of Nalidixic Acid by Coadministration with Fenbufen in Rats

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The change in rat serum, brain and cerebrospinal fluid (CSF) concentration-time profiles, and serum protein binding of nalidixic acid (NA) caused by fenbufen was studied. Periodically following the bolus i.v. administration of NA (10 mg/kg) alone or with fenbufen (20 mg/kg) to 10-week old male Wistar rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the rat sacrificed by microwave irradiation. Serum (total and unbound), brain and CSF levels for the drug were determined by HPLC method. Serum levels for NA declined mono-exponentially with time in both groups, and coadministered fenbufen caused a significant duration in the serum level for the quinolone. The fraction of NA bound to serum protein was hardly affected by fenbufen. In both groups, brain and CSF levels for NA rose quite rapidly after drug administration and then declined along with the serum levels. Even in the group given NA alone, both brain and CSF levels for the quinolone were considerably high, yielding approximately 1.4 and 1.1 as the ratio to the serum unbound levels, respectively. Fenbufen was found to increase these brain and CSF concentrations significantly to exactly the same extent as observed in serum levels, showing no change in the ratio of brain (about 1.4) or CSF (about 1.1) concentration to serum unbound concentration for NA from the ratio obtained for NA alone. These results indicate that the duration of the brain or CSF level for NA in the coadministered group was merely due to the increase in the serum level for NA and that fenbufen did not affect the permeability of NA into the CNS.
日本医療薬学会の論文
1994-06-20

Increases in Serum, Brain and Cerebrospinal Fluid Levels of Nalidixic Acid by Coadministration with Fenbufen in Rats

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