3-Chloro-4-(phenylsuccinimido)-benzenesulfonamide (GS 385), a new anticonvulsant: its quantitative determination, pharmacokinetics and metabolism using high performance liquid chromatography

Arzneimittelforschung. 1979;29(10):1583-8.

Abstract

A high-performance liquid chromatographic method (HPLC) involving dual wave length detection was developed for the determination of a new anticonvulsant, 3-chloro-4-(phenylsuccinimido)-benzenesulfonamide (suclofernide, GS 385, Sulfalepsin), and three of its metabolites: 3-chloro-4-(p-hydroxyphenylsuccinimido)-benzenesulfonamide (I), 3-chloro-4-(3'-phenylsuccinamyl)-benzenesulfonamide (II) and 3-chloro-4-(2'-phenylsuccinamyl)-benzenesulfonamide (III). The concentrations of GS 385 in blood samples from epileptic patients under chronic treatment with this drug was found in the range of 8--11 micrograms/ml. Pharmacokinetic curves of GS 385 blood levels in rats receiving single doses of the drug showed a maximum concentration of 22--23 micrograms/ml 1.5 h after oral application. The quantity of GS 385 in rat feces, bile and brain was also estimated. The p-hydroxy (I) and acid (II, III) metabolites of GS 385 were detected in both rat feces and bile, whereas only the acid metabolites were found in rat urine.

MeSH terms

  • Animals
  • Anticonvulsants / metabolism*
  • Bile / metabolism
  • Chromatography, High Pressure Liquid
  • Feces / analysis
  • Kinetics
  • Male
  • Methods
  • Rats
  • Succinimides / metabolism*
  • Sulfonamides / metabolism*
  • Time Factors

Substances

  • Anticonvulsants
  • Succinimides
  • Sulfonamides