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We test compounds for efficacy in vitro using concentrations
calculated on a molar basis but then switch to mg/kg dosing in
animals. Does anyone have any advice on the benefits of using molar
dosing (if any) rather than the conventional mg/kg when comparing
experimental compounds (of related but different molecular weights)
for efficacy in vivo?
Cheers
Keith
Keith Dredge
Preclinical Scientist
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Keith,
Molar dosing would help you to correlate in vivo efficacy results
with in vitro efficacy results as well as with CYP inhibition and
induction assay results.
regards,
Jignesh S. Kotecha
Scientist 1
Bioanalytical Division,
BE Centre,TRC.
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Molar dosing also corrects for possible salt weight. Dosing per kg
or by total dose may need to be corrected to the free form molecular
weight.
Pete bonate
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Molar dosing is the correct (logical) way to express things.
Unfortunately too many people would not be able to follow it. For
instance two compounds are administered at 10 mg/kg and the one
compound has MW of 250 and the other 1250. If they have the same
efficacy, the latter molecule is 5 times more potent. This could be
seen directly if one used molar dosing.
Stefan
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The following message was posted to: PharmPK
I agree with Stefan that molar dosing in medicine has great appeal in
logic
but aren't the clinical benefits difficult to discern? For example
where is
the correlation between potency and clinical characteristic amongst
the the
opiate type analgesics or antibiotics ? The most potent molecules like
buprenorphine and fentanyl are not the longest acting or the most
difficult
to reverse ..I realise that many molecules will have been discovered and
rejected precisely because they are too long acting or too difficult to
reverse with nalorphine, but to adopt the method even in clinical
pharmacology, we need more cogent reasons.
It's a bit like the old Florentine money system based on 12 instead
of 10.
It is logically appealing for its profusion of simple factors and
fractions,
but I can count on one hand the number of countries that would adopt it.
Andrew Sutton
Guildford Clinical Pharmacology Ltd.
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The following message was posted to: PharmPK
You may be interested to know that there is a Clinical Biochemistry
discussion site in the UK and a month or so ago they were discussing
units of measurements and ensuring that there is some uniformity
amongst laboratories. The consensus was to use mass rather than SI
units (OK, I know there will be the odd exception), not necessarily
solely because we dose in mg rather than moles, but that was one of
the factors. I am not sure of the origins of the present discussion
on this site, but I would always want to dose in mg. I can envisage
a mg but not a mole.
Graham Mould
Graham Mould, MRPharmS, PhD
Operations Director
Email: gmould.aaa.gcpl.co.uk
Guildford Clinical Pharmacology Unit Ltd. (GCPL)
Unit 35, Surrey Technology Centre
Surrey Research Park, Occam Road
Guildford, Surrey GU2 7YG
www.gcpl.co.uk
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