3-Chloro-4-(phenylsuccinimido)-benzenesulfonamide (GS 385), a new anticonvulsant: its quantitative determination, pharmacokinetics and metabolism using high performance liquid chromatography.
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.
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000032:analysis; D007700:Kinetics; D008297:Male; D008722:Methods; D051381:Rats; D013388:Succinimides / Q000378:metabolism*; D013449:Sulfonamides / Q000378:metabolism*; D013997:Time Factors
D000927:Anticonvulsants; D013388:Succinimides; D013449:Sulfonamides