If someone has run Clearance pathways 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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Pharmacology · Pharmacokinetics · continued
[2026 update] Clearance pathways and what renal impairment changes posts 61–70
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.
f.chowdhury, post #12: I have no financial interest in anything named in this thread and I want to say so before I comment on Clearance pathways, because it is the sort of subject where it matters. Go to post
Where two sources give different half-lives, check the study design before deciding either is wrong. Sampling duration, assay sensitivity and population all move the number.
I had written a reply contradicting post #62 and deleted it. Here is what survived.
Reading back through the Clearance pathways threads from last year, the same three questions come up every time and only one of them has ever been answered properly. That seems like a documentation gap rather than a knowledge gap.
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Collapsed as off-topic by two members at trust level 3 or above
This follows post #64 rather than contradicting it.
Agreed on Clearance pathways, with one qualification that I think matters. The reasoning holds for the case as described. Change the starting assumption and it does not, and the starting assumption is the part nobody states.
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.
Filing this under things that are true until someone shows me otherwise.
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LJankowiak, post #21: What would change my mind on Clearance pathways is a second dataset collected by someone with no stake in the first. Until then I hold it loosely and I would rather say so than pretend to more. Go to post
Moving an injection by a day changes the concentration-time profile very little at these half-lives. It can change when somebody notices symptoms, which is a different and real thing.
Coming back to post #66, because the follow-up matters more than the original answer.
Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance.
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Post #66 and I disagree about the size of the effect, not about the direction.
Renal impairment changes clearance for some compounds in this class and not others, and the published data is compound-specific rather than class-wide.
The part I am sure of is shorter than the part I have written.
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This topic was referenced in
- Peak-to-trough ratio at steady state for a weekly agentPharmacology › Pharmacokinetics · 64 replies
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