Pharmacokinetics and Pharmacodynamics of XXXX Administered Through an External Ventricular Drain.

@entity1 @entity548 @entity510 @entity1456 @entity439
BACKGROUND: @entity548 ( @entity548 ) frequently complicates spontaneous intracerebral or @entity510 ( @entity510 ). Administration of intraventricular @entity1456 (TPA) accelerates blood clearance, but optimal dosing has not been clarified. Using a standardized TPA dose, we assessed peak cerebrospinal fluid (CSF) TPA concentrations, the rate at which TPA clears, and the relationship between TPA concentration and biological activity. METHODS: Twelve @entity1 with @entity439 @entity510 and @entity548 , treated with endovascular coiling and ventricular drainage, were randomized to receive either 2  mg intraventricular TPA or placebo every 12  h (five doses). CT scans were performed 12, 48, and 72  h after initial administration, and blood was quantified using the @entity510 Sum and @entity548 Scores. CSF TPA and fibrin degradation product (D-dimer) concentrations were measured at baseline and 1, 6, and 12  h after the first dose using ELISA assays. RESULTS: Median CSF TPA concentrations in seven TPA-treated @entity1 were 525 (IQR 352-2129), 323 (233-413), and 47 (29-283) ng/ml, respectively, at 1, 6, and 12  h after drug administration. Peak concentrations varied markedly (401-8398  ng/ml). Two @entity1 still had slightly elevated levels (283-285  ng/ml) when the second dose was due after 12  h. There was no significant correlation between the magnitude of CSF TPA elevation and the rate of blood clearance or degree of D-dimer elevation. D-dimer peaked at 6  h, had declined by 12  h, and correlated strongly with radiographic @entity548 clearance (r  =  0.82, p  =  0.02). CONCLUSIONS: The pharmacokinetics of intraventricular TPA administration varies between individual @entity1 . TPA dose does not need to exceed 2  mg. The optimal administration interval is every 8-12  h.
