PK parameters from multiple doses [PK / PD]

posted by Helmut Homepage – Vienna, Austria, 2017-11-19 10:24 (1036 d 17:37 ago) – Posting: # 17991
Views: 7,354

Hi Jeewaka,

» […] a PK study where multiple doses are given […] to estimate the PK parameters of the single dose from the blood concentrations of multiple dosing.
» is this possible?

Not easy. You could only perform modeling assuming (!) linear PK (clearance will not change over time). Given your sampling schedule I guess it will be very difficult to model anything beyond a simple one compartment model (e.g., ≥2, Michaelis-Menten elimination, circadian rhythms influencing the PK after the morning/evening doses, saturation of metabolising enzymes after accumulation, auto-induction or inhibition …). Even then you get only PK parameters describing the overall behaviour of the drug – not “of the single dose”. See this example of auto-induction (slides 21–22). With your sampling schedule I guess it would be impossible.* Next time I strongly suggest to sample at the pre-doses to get an idea. Much better to sample after the first dose as well.

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