This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Half-life determines how quickly concentration approaches steady state and does not determine what the steady-state concentration is. Dose and clearance determine that.
Same conclusion as the reply above, reached differently, which is mildly reassuring.
I would keep half-life and the decision it usually gets used for separate in this thread. They are related and they are not the same question, and merging them is why the last one went badly.
On half-life the community has more anecdote than the confidence in this thread implies, and I include my own contribution in that.
A pharmacokinetic model fitted to trial data describes the population studied. Applying it to somebody outside the enrolled range is an extrapolation, and the model will not tell you it is.
It is the sort of thing that seems obvious in retrospect and was not at the time.
Steady state is approached in roughly four to five half-lives. For a compound with a week-long half-life that is four to five weeks, which is where the escalation interval in the trials comes from.
That has been true for the cases I have seen and I have not seen many.
Post #127 is right about the mechanism and I think understates the practical bit.
Metabolism for peptide drugs is proteolytic rather than hepatic in the usual sense, which is why the cytochrome interaction questions that dominate small-molecule pharmacology mostly do not apply.
Half-life looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.
If someone has run half-life properly I would rather read that than my own reconstruction of it. Posting mine only because the thread has gone quiet.
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