Bioequivalence and Bioavailability Forum

Dear Nirali!

❝ Dear Sir,

Don’t forget the Madams on the forum!

❝ Which method should be used for Cpd analysis to prove steady state? Study has been conducted for EU regulatory.

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There’s no guideline for human studies and not even a consensus amongst scientist.
Maybe one of my lectures (slides 27/28) helps.
The only regulatory document I know of is FDA’s veterinary bioequivalence guidance (Oct 2006):

When conducting a steady-state investigation, data on the minimum drug concentrations (trough values) observed during a single dosing interval (CMIN) should also be collected. Generally, three successive CMIN values should be provided to verify that steady-state conditions have been achieved. Although CMIN most frequently occurs immediately prior to the next successive dose, situations do occur with CMIN observed subsequent to dosing. To determine a steady state concentration, the CMIN values should be regressed over time and the resultant slope should be tested for its difference from zero.

(my emphases)

For another approach see also the mixed effects model in Chow & Liu’s textbook (all editions).