Bioequivalence and Bioavailability Forum

Dear VG,

❝ How to calculate Cmin manually.

Cmin is a steady state parameter – It is the minimum or “trough” concentration (Cmin) of a drug observed after its administration and just prior to the administration of a subsequent dose. (Units -Amount/Volume).

Cmin can be calculated manually from the obtained Bio-anlaytical concentration data - The first measured concentration of drug after the drug administration is the Cmin concentration for first dose and last measured concentration of the first dose will be the Cmin for the second dose of drug and the last measured concentration of the second dose will be the Cmin for the third dose … (steady state).

Formulae for calculating Cmin = Accum x Intercept x (e-lzT - e-kaT)

❝ What are the input data required for Cmin calculation.

Input data for PK analysis will be the Bio-analytical data for Cmin calculation by using PK software. Manual procedure is already stated above.

❝ What is the current thinking of Cmin with regards to 90 % CI as per current EMA requirements. Is it to be calculated or not?

As per current EMA guideline

Cmin is not needed to be calculated for Immediate release formulation with regards to 90% CI (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr) reference

Cmin is to be calculated for Modified release formulation with regards to 90% CI (Modified release guideline - CPMP/EWP/280/96 Corr) reference
If the reference links does not work, please input italic words in the google to find the reference articles.

Regards,
RVR