Intrathecal (i.t.) administration of monoclonal antibodies (mAbs) represents a new therapeutic approach for the treatment of @entity5 , which is rapidly fatal. This study describes the pharmacokinetics of intrathecally administered mAbs in @entity35 and monkeys to optimize their use for regional antineoplastic therapy. We hypothesized that mAbs, which are high-molecular-weight, polar compounds, would be eliminated from the cerebrospinal fluid (CSF) at the same rate as bulk flow of CSF. We found that an IgM mAb was cleared from @entity35 CSF at the rate of CSF bulk flow (0.0041 ml/min), but an IgG mAb was cleared at a faster rate (0.011 ml/min). We attempted to reduce the CSF clearance of an IgG mAb by administration of @entity3791 and @entity1483 , which inhibit the rate of CSF production and CSF bulk flow. We demonstrated that the administration of @entity3791 and @entity1483 reduced the clearance of IgG mAb from @entity35 CSF by 58%. These results establish that bulk flow of CSF determines a minimum rate of elimination from the CSF for IgM mAbs and that additional mechanisms operate to clear IgG mAbs from the CSF. Inhibition of CSF production by @entity3791 and @entity1483 increased the area under the CSF concentration vs. time curve of IgG mAbs in the CSF. The increased area under the CSF concentration vs. time curve is likely to improve the therapeutic index of these agents for i.t. therapy.

Pharmacokinetics of IgG and IgM anti-ganglioside antibodies in XXXX and monkeys after intrathecal administration.

@entity5 :: ('MESH:D009369', 'Disease') :: ['leptomeningeal cancer'] @entity3791 :: ('MESH:D000086', 'Chemical') :: ['acetazolamide'] @entity1483 :: ('MESH:D005665', 'Chemical') :: ['furosemide'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats']
@entity35 :: (10116,Species) :: ['rats']
