Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344232 (blurred vision)
 2,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ADD 94057, a metabolite of fluzinamide, manufactured by the A. H. Robins Company, blocks chemically- and electrically-induced seizures in animals. The primary objective of this open add-on study was to evaluate patient tolerability of ADD 94057 at ascending target plasma concentrations. Nine subjects with medically refractory seizures were receiving phenytoin (PHT, 3), carbamazepine (CBZ, 3), or both (3). A pharmacokinetic profile after a single oral 400-mg dose of ADD 94057 was used to calculate ADD 94057 dosages. After a 4-week baseline period, patients were treated for 4 weeks with weekly ADD 94057 dosage escalations. Two patients completed the study at their assigned highest dosage level; the other patients finished the study at lower dosages. The patients receiving PHT (but not CBZ) tolerated higher plasma concentrations of ADD 94057 than did patients receiving CBZ, alone or in combination with PHT. Adverse experiences included headache, ataxia, blurred vision, diplopia, dizziness, lightheadedness, and mild confusion. Eight of nine patients had reductions in seizure frequency from baseline.
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PMID:Pharmacokinetic and dose tolerability study of ADD 94057 in comedicated patients with partial seizures. 173 43

W-554 (ADD 03055, 2-phenyl-1,3-propanediol dicarbamate) has broad-spectrum antiepileptic activity in animal models of epilepsy. We evaluated its pharmacokinetics and toxicity as an adjunctive medication in eight adult male patients with uncontrolled seizures, treated with phenytoin (n = 4) or carbamazepine (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 toxicity (mild blurred vision and tremor) possibly attributable to W-554. Seizure control was improved in six of eight subjects, and seizures were less severe in three, while on W-554. Addition of W-554 resulted in increases in serum phenytoin levels, and small decreases in serum carbamazepine levels.
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PMID:Pharmacokinetics of W-554 (ADD 03055) in epileptic patients. 407 64