Prediction of steady-state bioequivalence relationships using single dose data I-linear kinetics.
Simulated data using a linear one- and two-compartment body model with different absorption characteristics were used to evaluate the ability of single dose bioavailability data to predict the relationships that exist at steady state. This was done by comparing the confidence intervals obtained from single and multiple dose data sets for the parameters of Tmax, Cmax, and area under the curve from time zero to infinity (AUC0-infinity). As a consequence of Tmax and Cmax decreasing and increasing from single to multiple dosing regimens, the confidence intervals for these parameters reflected these changes. The 90 per cent confidence interval expressed as a percentage of the reference mean increased or decreased for Tmax dependent upon the ratio of Ka test/Ka reference, and decreased for Cmax while the interval for AUC0-infinity exhibited no predictable pattern and appeared to be influenced by the amount of error in the data set. Alteration of either the dosing interval or the fraction absorbed did not affect the pattern of change in the confidence intervals for Tmax and Cmax, but the latter did result in a decrease in the interval for AUC0-infinity. Analysis of the confidence intervals for Tmax, Cmax and AUC0-infinity in bioequivalency studies for quinidine gluconate and procainamide hydrochloride following administration of single and multiple doses to different subjects appeared to be consistent with the patterns observed for the simulated data sets.
Jackson
A J
AJ
Division of Bioequivalence, Food and Drug Administration, Rockville, Maryland 20857.
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010599:Pharmacokinetics; D011342:Procainamide / Q000008:administration & dosage / Q000493:pharmacokinetics; D011802:Quinidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
D004364:Pharmaceutical Preparations; D011802:Quinidine; D011342:Procainamide; C016713:quinidine gluconate