BIOEQUIVALENCE - PERFORMANCE OF SEVERAL MEASURES OF RATE OF ABSORPTION

被引:58
作者
BOIS, FY
TOZER, TN
HAUCK, WW
CHEN, ML
PATNAIK, R
WILLIAMS, RL
机构
[1] UNIV CALIF SAN FRANCISCO,SCH PHARM,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143
[3] US FDA,CTR DRUG EVALUAT & RES,OFF GENER DRUGS,ROCKVILLE,MD 20855
关键词
D O I
10.1023/A:1018970901116
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The highest point of the plasma concentration-time profile, C-max, is currently used by regulatory agencies to assess the rate of drug absorption after single dose administration of oral products. It is, however, quite insensitive, and a number of new measures of rate have been proposed. Using simulations, several approaches toward measuring rate were tested. A set of model scenarios for drugs with typical mean characteristics and statistical distributions was investigated. Using different kinetic models of disposition, the time course of the concentration in plasma was simulated. Intraindividual and interindividual variability and assay error were modeled using Monte Carlo techniques. The accuracy, precision, and ease of use of the various measures of rate were evaluated by simulating crossover design clinical trials and then determining the probability of declaring bioequivalence as a function of differences in rates of absorption between test and reference formulations. All of the rate measures tested showed a degree of insensitivity to changes in rate and no universally superior measure was found. Indeed, the main conclusion is that the choice of a measure should be based on simulations of the particular situation in a bioequivalence trials.
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页码:966 / 974
页数:9
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