Right, and stated more narrowly than I would have dared to state it.
Where I part company with post #25, and it is a narrow parting.
The accumulation ratio for weekly dosing with a week-long half-life is around two, which is why the concentration after several doses is roughly double the concentration after the first.
Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.
One case, stated as one case.
Post #39 put the caveat in the right place and I want to underline it.
A missed weekly dose perturbs a slowly moving average rather than creating a trough. That is the pharmacokinetic reason the labelling does not recommend doubling.
Someone will know this better than I do and I hope they say so.
Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.
I have separated what I observed from what I concluded, which does not always happen.
Body weight affects volume of distribution and therefore exposure at a fixed dose. Whether that translates into a dosing implication depends on the width of the therapeutic window.
Dose proportionality across the studied range means dose arithmetic behaves the way you would naively expect. It is worth checking whether it holds for a given compound rather than assuming.
I have deliberately not rounded that, because the rounding is where the argument starts.
On post #97 — agreed on the reasoning, with one qualification.
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.
Coming back to post #102, because the follow-up matters more than the original answer.
The accumulation ratio for weekly dosing with a week-long half-life is around two, which is why the concentration after several doses is roughly double the concentration after the first.
Read the full topic (111 posts)
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