Pharmacokinetics of W-554 (ADD 03055) in epileptic patients

Epilepsia. 1985 Nov-Dec;26(6):602-6. doi: 10.1111/j.1528-1157.1985.tb05699.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Carbamazepine / adverse effects
  • Carbamazepine / blood
  • Carbamazepine / therapeutic use
  • Drug Interactions
  • Epilepsy / blood
  • Epilepsy / drug therapy*
  • Felbamate
  • Half-Life
  • Humans
  • Kinetics
  • Male
  • Phenylcarbamates
  • Phenytoin / adverse effects
  • Phenytoin / blood
  • Phenytoin / therapeutic use
  • Propylene Glycols / adverse effects
  • Propylene Glycols / blood
  • Propylene Glycols / therapeutic use*

Substances

  • Phenylcarbamates
  • Propylene Glycols
  • Carbamazepine
  • Phenytoin
  • Felbamate