INTRA-SUBJECT AND INTER-SUBJECT VARIABILITIES OF CGP-33101 AFTER REPLICATE SINGLE ORAL DOSES OF 2 200-MG TABLETS AND 400-MG SUSPENSION

Purpose. The purpose of this study was to use a replicate designed tri al to assess the overall, intra- and inter-subject variabilities in ph armacokinetic parameters of CGP 33101 after oral administration of tab lets relative to that of powder suspended in water, and to determine t he relative proportion of the intra-subject variance to the overall va riability. 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 331 01 was characterized in terms of C-max, T-max, and AUC. Bioavailabilit y of tablets relative to suspension and intra- and inter-subject varia bility were assessed by statistical analysis. Results and Conclusions. The overall variabilities in absorption kinetics of CGP 33101 in heal thy subjects were small with CV's of the population mean values for AU C and C-max less than 26% for both tablets and suspension. Contributio n of intra-subject variability to the overall variability was also sma ll (similar to 20%). Both the overall and intra-subject variabilities of AUC and C-max 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 absorp tion based on 90% conventional confidence intervals (for AUC and C-max ) and Wilcoxon rank-sum test (for T-max).