Intra- and inter-subject variabilities of CGP 33101 after replicate single oral doses of two 200-mg tablets and 400-mg suspension.
OBJECTIVE
The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability.


METHODS
Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of Cmax, Tmax, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis.


CONCLUSIONS
The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and Cmax less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (approximately 20%). Both the overall and intra-subject variabilities of AUC and Cmax after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p > 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and Cmax) and Wilcoxon rank-sum test (for Tmax).
Cheung
W K
WK
Bioanalytics and Pharmacokinetics, Ciba Pharmaceuticals Division, Summit, New Jersey 10502, USA.
Kianifard
F
F
Wong
A
A
Mathieu
J
J
Cook
T
T
John
V
V
Redalieu
E
E
Chan
K
K
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide