W-554 ( @entity2807 , @entity2807 ) has broad-spectrum antiepileptic activity in animal models of @entity302 . We evaluated its pharmacokinetics and @entity137 as an adjunctive medication in eight adult male @entity1 with uncontrolled @entity410 , treated with @entity3174 (n = 4) or @entity2049 (n = 4). After a single 200-mg dose, peak W-554 serum levels of 2.65-4.10 mg/L were achieved in 1-4 h. Half-lives were 11.2-16.1 h and clearance varied from 34.2-64.6 ml/h X kg. The apparent volume of distribution was 0.726-1.046 L/kg. Chronic dosing at 400, 800, 1,200, and 1,600 mg/day resulted in median steady-state trough levels of 5.1, 10.2, 14.6, and 20.3 mg/L. A second kinetic study at the end of chronic dosing indicated no change in volume of distribution, decreased clearance, and increased half-life, compared with single dose data. Urinary excretion of unchanged drug was 13.8-28.6% of the dose. Only one subject had @entity137 ( @entity227 and @entity400 ) possibly attributable to W-554. @entity410 control was improved in six of eight subjects, and @entity410 were less severe in three, while on W-554. Addition of W-554 resulted in increases in serum @entity3174 levels, and small decreases in serum @entity2049 levels.

Pharmacokinetics of W-554 ( @entity2807 ) in XXXX @entity1 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizures', 'Seizure'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity227 :: ('MESH:D014786', 'Disease') :: ['mild blurred vision'] @entity400 :: ('MESH:D014202', 'Disease') :: ['tremor'] @entity302 :: ('MESH:D004827', 'Disease') :: ['epilepsy'] @entity3174 :: ('MESH:D010672', 'Chemical') :: ['phenytoin'] @entity2807 :: ('MESH:C047360', 'Chemical') :: ['2-phenyl-1,3-propanediol dicarbamate', 'ADD 03055'] @entity2049 :: ('MESH:D002220', 'Chemical') :: ['carbamazepine']
@entity302 :: (MESH:D004827,Disease) :: ['epileptic']
