This figure shows the 24-hour excretion rate in a typical bioequivalence study of potassium chloride tablets. The figure is a plot of the excretion rate versus the midpoint of the urine collection interval, and the plots are from test subjects in period 1, reference subjects in period 1, test subjects in period 2 and reference subjects in period 2. There's a small amount of fluctuation during the day and this may be due to meals or it may be due to circadian rhythms or a combination of those. However, as you can see in the figure, the 24-hour baseline is consistent from period 1 to period 2 and in the test and reference subjects.
So the first case study that I'll discuss I'll call formulation A, and it's for a 20 milliequivalent extended release tablet product. For this particular product, without baseline correction, both the amount excreted over 24 hours and Rmax met the 90 percent confidence interval criteria. However, with baseline correction, Rmax, the maximal rate of excretion, did not meet the 90 percent confidence interval criteria. Therefore, we found the application unacceptable.
This chart shows the 90 percent confidence