Bioequivalence and Bioavailability Forum

Dear Mr Rana,

Kindly follow forum policy, see here

Cmin,ss: Minimum steady-state plasma drug concentration during a dosage interval

Ctrough: Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration])

Dear Rana,

please search the forum in the future.

It’s a matter of terminology. Commonly^1,2 C_trough is defined as the concentration at the end of the dosage interval τ and C_min,ss as the (global) minimum within τ. FDA³ defines C_min as the concentration at τ. EMA⁴ wants to see C_min,ss, but quotes the definition of C_trough (“By C_min,ss we mean the concentration at the end of the dosage interval, i.e. [sic] C_trough”).^*
Pharsight’s Phoenix/WinNonlin reports the global minimum. For the FDA and EMA you have to either use C_last instead or – if you are courageous – consider using an estimate (if there are time deviations from τ or missing samples and you have a suitable estimate of λ_z). For details see the previous posts or this presentation (slides 34-39).

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1. HJ Weimann
   Drug concentrations and directly derived parameters
   In: W Cawello (Ed.), Parameters for Compartment-Free Pharmacokinetics
   Shaker-Verlag, Aachen pp 31–4 (2003)
   
2. AGAH working group PHARMACOKINETICS
   Collection of terms, symbols, equations, and explanations of common pharmacokinetic and pharmacodynamic parameters and some statistical functions
   Arbeitsgemeinschaft für Angewandte Humanpharmakologie (AGAH), 2004
   
3. Food and Drug Administration, Center for Drug Evaluation and Research (CDER)
   Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations
   Rockville, March 2003
   
4. European Medicines Agency
   Overviews of Comments received on Draft Guideline on the Investigation of Bioequivalence
   Doc. Ref. EMA/CHMP/EWP/26817/2010
   London, 20 January 2010

• By apple we mean the spheric fruit others call orange.