Progabide-induced changes in carbamazepine metabolism.
Carbamazepine (CBZ) and carbamazepine 10,11 epoxide (CBZ-E) concentrations were measured during a safety and efficacy trial of progabide. The average CBZ and CBZ-E serum concentrations were calculated from serial measurements during placebo and active treatment periods. Significant decreases in CBZ and significant increases in CBZ-E were observed after the first dose of progabide, and these changes persisted during 3 months of active treatment. Ninety-five percent of the patients had increases in the epoxide/CBZ ratio at the end of 3 months of treatment. These changes are consistent with displacement of CBZ from protein binding sites and inhibition of CBZ-E metabolism induced by progabide and are analagous to the interaction between valproate and CBZ.
Graves
N M
NM
University of Minnesota, College of Pharmacy, Minneapolis 55455.
Fuerst
R H
RH
Cloyd
J C
JC
Brundage
R C
RC
Welty
T E
TE
Leppik
I E
IE
D000293:Adolescent; D000328:Adult; D002220:Carbamazepine / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D004311:Double-Blind Method; D004347:Drug Interactions; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use
D010919:Placebos; D002220:Carbamazepine; C017985:progabide; D005680:gamma-Aminobutyric Acid