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posted by Helmut Homepage – Vienna, Austria, 2010-11-13 14:47 (3726 d 21:53 ago) – Posting: # 6146
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Dear Luv(blooms)!

One additional note: Check the time-course in a multiple dose study as suggested by Yung-jin in his first post. If you don’t see a deviation from linear PK, stop worrying about trying to fit any (!) model. If a change in clearance(s) is not reflected in plasma concentrations, no model will work (i.e. converge).

Example modified from Danielsson/Weiner (4th ed. pp. 684–90), Autoinduction, two-compartment PK.


Single dose study; 1 h infusion of 40 mg (bottom left). It was decided based on a simulation (top green line) to start the multiple dose study with a 1 h infusion of 120 mg as a loading dose, followed by 0.5 h infusions of 40 mg (τ = 8 h). What we see, is autoinduction which lead roughly after the second day to equilibrium of only ≈50 % of predicted from the simple model (without autoinduction).

Dif-tor heh smusma 🖖
Helmut Schütz

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