Pharmacokinetics of felbamate in pediatric and adult beagle dogs.
The relative bioavailability and pharmacokinetics of felbamate (FBM) after a single oral dose and after 10 once-daily oral doses of 60 mg/kg were investigated in adult and pediatric dogs of both sexes. The pediatric and adult dogs were aged 4-6 weeks and 1-2 years, respectively. Analysis of variance (ANOVA) was performed on the bioavailability parameters among all groups and between the first and last doses. No sex-related differences in bioavailability and pharmacokinetic parameters were observed. The bioavailability of FBM in pediatric dogs was significantly less as compared with that in adult dogs. Rapid overall elimination of the drug in pediatric dogs appears to be responsible for the lower bioavailability. The bioavailability of FBM after the last dose was also significantly lower than after the first dose for both age groups. No major differences in the rate constant of FBM absorption (ka) and volume of distribution at steady state (VSS) were observed between the two age groups. As with other clinically useful antiepileptic drugs (AEDs), higher doses of FBM may be required in pediatric populations to achieve optimum drug levels, assuming that age-related changes in FBM disposition will also be confirmed in humans.
Adusumalli
V E
VE
Department of Biochemistry, Wallace Laboratories, Cranbury, New Jersey 08512.
Gilchrist
J R
JR
Wichmann
J K
JK
Kucharczyk
N
N
Sofia
R D
RD
D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004285:Dogs / Q000097:blood*; D000078328:Felbamate; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012737:Sex Factors
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D000078328:Felbamate