Distribution of the anticonvulsant felbamate to cerebrospinal fluid and brain tissue of adult and neonatal rats.
The concentrations of felbamate (FBM) and its three metabolites were determined in plasma, cerebrospinal fluid (CSF), and brain tissue of adult and neonatal rats that received single oral doses of FBM at amounts varying from 250 to 2000 mg/kg for adults and from 100 to 500 mg/kg for neonates. The increase in plasma Cmax and AUC0-24 with the dose was less than proportional in both age groups. The highest plasma Cmax in adults dosed with 2000 mg/kg was 140.3 micrograms/ml; in neonates dosed with 500 mg/kg it was 257.0 micrograms/ml. The maximum brain concentrations for these dosages were 90.9 and 220.4 micrograms/g, respectively. The average brain/plasma, CSF/plasma, and brain/CSF partition coefficients for the drug were 0.64, 0.55, and 1.16 for adults and 0.83, 0.67, and 1.23 for neonates, respectively. No statistically significant change of the partition coefficients with time or dose was observed (p < 0.05). Very good linear correlations between FBM plasma concentrations and concentrations in CSF and brain tissue were obtained (r2 > 0.98). Only the 2-hydroxy metabolite was present in considerable amounts in plasma and brain tissue of the high-dose groups of both ages.
Adusumalli
V E
VE
Wallace Laboratories, Division of Carter-Wallace, Inc., Cranbury, NJ 08512.
Wichmann
J K
JK
Kucharczyk
N
N
Sofia
R D
RD
D000284:Administration, Oral; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D000927:Anticonvulsants / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000078328:Felbamate; D005260:Female; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate