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Dear All,
I know this subject has been covered extensively, and before you ask, I
have read a few (recommended PKarchive) articles to aid my
understanding.
It is a Monday morning.
Although simple to most of you, I am struggling to get to grips with
the key points to consider when trying to predict inter-species PK
behaviour of a specific compound.
I have a NCE with the following PK characteristics in an average MF-1
mouse after iv bolus dose 1mg/kg:
Co/max = 1.667ug/ml
Clp = 0.66ml/min
Vd= although high for TBW, is calculated at 0.123L
It is thought that excretion is predominantly via renal filtration of
the unchanged parent molecule.
Basically, all I need to do is approximately predict the dose required
to achieve the same plasma concentration in an average 70kg human. Can
this be done?
Obviously I do not have a model to hand, but can you tell me if I need
to focus on scaling up the specific clearance parameter presuming that
elimination route/pathway is the same in the human.
Therefore should I take into account differences in TBW/ Vd/ GFR values
and obviously weight? Studies have used MLP and neoteny as exponential
factors with varying degrees of success, how important are they for my
application?
All help is most appreciated
Many Thanks
Simon
*********************************************
Simon Clark M.Sc.
DMPK Specialist
Analytical Pharmacology,
Antisoma Research Laboratories,
St Georges Hospital Medical School,
Cranmer Terrace,
London SW17 0QS.
Direct +44 (0)20 8772 7071
simon.clark.aaa.antisoma.com
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)