Bioequivalence and Bioavailability Forum

❝ I read in a PK report: "Where less than 3 quantifiable concentrations, AUC is not reported."

❝ The way I see it, if you only have two sequential concentrations above quantifiable limit, then you can generate a Tmax, but you can't be sure of the accuracy of Tmax, especially if Cmax is barely above quantitation limit of the assay used.

• EMA (2010)
  A sufficient number of samples to adequately describe the plasma concentration-time profile should be collected. The sampling schedule should include frequent sampling around predicted t_max to provide a reliable estimate of peak exposure. In particular, the sampling schedule should be planned to avoid C_max being the first point of a concentration time curve. The sampling schedule should also cover the plasma concentration time curve long enough to provide a reliable estimate of the extent of exposure which is achieved if AUC_(0–t) covers at least 80% of AUC_(0–∞). At least three to four samples are needed during the terminal log-linear phase in order to reliably estimate the terminal rate constant (which is needed for a reliable estimate of AUC_(0–∞)).
  
• FDA (ANDA draft 2013)
  We recommend drawing blood samples at appropriate times to describe the absorption, distribution, and elimination phases of the drug. For most drugs, we recommend collecting 12 to 18 samples, including a predose sample, per subject, per dose. This sampling should continue for at least three or more terminal elimination half-lives of the drug. The exact timing for sample collection depends on the nature of the drug and the rate of input from the administered dosage form. The sample collection can be spaced in such a way that the maximum concentration of drug in the blood (C_max) and terminal elimination rate constant (K_el) can be estimated accurately. At least three to four samples should be obtained during the terminal log-linear phase to obtain an accurate estimate of λ_z from linear regression.