The transport of gentamicin in the choroid plexus and cerebrospinal fluid

Gentamicin often attains inadequate therapeutic levels in cerebrospinal fluid (CSF). In the present study, the possibility that gentamicin might be transported from CSF to blood by a mechanism in the choroid plexus was investigated. Rabbit choroid plexuses were incubated 15 to 120 minutes in artificial CSF containing 14C-gentamicin and 3H-inulin. The choroid plexuses accumulated gentamicin linearly up to 120 minutes where a tissue/medium ratio of 5.4 was attained. Uptake of gentamicin was inhibited by: 1) increasing the gentamicin concentration or adding kanamycin; 2) omitting oxygen and glucose; 3) adding dinitrophenol to the medium; 4) incubating at 4 degrees C; OR 5) incubating in rabbit CSF. However, uptake was not inhibited by probenecid or ammonium ion. Kinetic analysis revealed that gentamicin was transported into choroid plexus by a process that satisfied Michaelis-Menten kinetics. A Lineweaver-Burk transformation of the transport values for the saturable component yielded a Kt of 51.8 mug/ml and a Vmax = 1.8 mug/ml/min. In vivo, gentamicin clearance from CSF, although saturable, was only 1.4 times greater than inulin because of the relatively low Kt and Vmax of the choroid plexus transport system for gentamicin and the presence of inhibitors of gentamicin transport in rabbit CSF. We conclude that the saturable transport of gentamicin from CSF, although quantitatively not large, is a factor in determining gentamicin levels in CSF.