We are planning to give a SC dose or IM dose to humans each in a single site at volumes of 1 mL and 2 mL, respectively. The drug is waterBack to the Top
soluble so the formulation will be PBS or similar.
Prior to going to man, a rabbit PK study will be performed with equal
doses (mg) by IV, SC, and IM routes.
Intended dose in man is 20 mg SC in 1 mL or 20 mg in 2 mL IM (depends
on stability issues, etc)
How would you suggest I scale down dose and volume to the rabbit (no PK in rabbit yet). Use weight adjusted values or ?
20mg/70 kg 0.29 mg/kg
1 mL/70 kg 0.014 mL/kg
2 mL/70 kg 0.028 mL/kg
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U can scale down the doses by taking surface area ratio's of man to
Surface area ratio of 70 kg man to 1.5 Kg Rabbit is 0.07
So now you can multiply 20 mg human dose with 0.07 and it will be 1.4 mg
of actual dose in 1.5 Kg rabbit which is equivalent to 0.93mg/kg.b.wt
Now you can take 0.93 mg/ml solution for sc dosing (1ml/kg) and 0.47mg/ml
for IM dosing (2ml/kg). I think this may help u.
Glenmark Pharmaceuticals LTD.
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For calculating dose in rabbit I suggest to apply conversion factor from
human dose to rabbit.
You can find tables with conversion factor in the draft guidance of the
"Estimating the safe starting dose in clinical trials for therapeutics
adult healthy volunteers" from the FDA web page. By the way, Who knows
about the current status of this guidance? Comments from Pharmaceuticals
and CROs to this draft were too hard to expect a totally new guidance
happen... i.e. considering PK and PK/PD modeling in doses selection, a
subject of this PhamPK list.
Please, note that accordingly with your proposal of 20 mg/ 70 kg = 0.29
mg/kg the dose in rabbit would be 0.29 mg/kg x 1.8 kg (rabbit weight) =
However, following other approaches, as a conversion factor procedure,
in rabbit would be three times higher (above 1.5 mg).
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