Religious debate [Regulatives / Guidelines]

posted by Helmut Homepage – Vienna, Austria, 2016-02-12 17:04 (1955 d 16:02 ago) – Posting: # 15985
Views: 13,829

Hi nobody,

» » Ahem. What to you mean by nonsense – apart from the word “terminal”?
»
» I don't like this parameter, it's often used/compared in senseless ways. Clearance, volume, f is closer to the clinical reality. But doctors (and many others) can handle "times" (hours), but not "liters per hour" (but AUC divided by dose they find highly intuitive, which is 1/clearance ... :-D )

On David Bourne’s PKPD-list we have the annual religious debate (aka chicken vs. egg). The thread “A question of clearance” (part 1: 2009, part 2: 2010) set the record since 1995 (!) with an amazing 152 posts. I don’t belong to any of the churches (parameterization of models in terms of rate constants or clearances).
Both are mechanistic and purely empirical. Volume(s) of distribution and clearance(s) are theoretical constructs as are rate constants. Is the body a well-stirred beaker? C’mon! This is the fundamental (but delusionary) world of both churches. I can’t agree that any of the parameters is “closer to the clinical reality”. There is one exception: Hemodialysis, where the volume of distribution chances. This is the only case where I tend to lean towards the V & CL-church. In all other cases and when it comes to NCA [sic] I’m happy with both.
What I definitely don’t like is that PK software in evaluating data of an extravascular dose spit out CL/ƒ, V/ƒ, etc. Since ƒ is unknown, this kind of “information” is meaningless. When I review manuscripts I have a polite boilerplate for that. :-D

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