Hi Shubham,

The dose for animal studies should be decided based on LD50 of the compound, I am assuming here you have synthesized a compound.

The dose and calculations depend on

Body weight of the animal

Therapeutic dose and indication

Drug physicochemical profile

LD50

Body surface area

Could be tailored from human dose

Depends on the route of administration.

Check some preclinical literature and conversion tools by pubmed, google scholar, science direct.

https://www.targetmol.com/pages/dosage

Hope this helps.

Hi,

Sounds like a basic question but is very often asked by experienced scientists. The answer is it depends on your goal. Measurement PK does not always mean analysis 'only' PK so the dose will be different if:

• specific aspects of the PK profile are analyzed (or model establishment)
• pharmacokinetics or toxicokinetics
• PK variability
• comparison with homolog or another route of adm
• route of administration (bioavailability)
• presence of specific effects like flip-flop kinetics
• double peak phenomena after a single dose
• local/general tolerance
• pilot analysis
• number of doses
• range of linear PK
• cumulation, deep compartments
• first, the pass effect
• percent of blood plasma proteins binding
• study item (biologics, biotech, prodrugs, synthetics)
• additional PD observations
• immunogenicity if appropriate (ADA, NAbs control)

And many others factors and goals may change decisions about dose amount. But one critical is a range of validation of your analytical method. If for example, LLOQ of your method is 10 ng/mL you can't use a dose that gives concentrations between 0.01-3.0 ng/mL. Consequently in your PK study:

• Cmax should be slightly lower (variability of PK) than the HLOQ of the method
• Clast should be slightly higher than the LLOQ of the method
• Clast should be close or more than 20 x lower than Cmax
• If blood volume is 7% of the BW then you can calculate concentration at time point = 0 (Cmax if the iv bolus is used) based on this volume and study item amount you can calculate more less concentration close to Cmax. In the rat (300 g) blood volume is circa 21 mL.

Please remember that the calculation is very very general because depending on study item many processes may change this value within seconds (blood protein binding, first-pass effect, route of administration, and presence of absorption phase etc). So if possible always if you have no data which can be translated from other animals or homologs try to make a pilot study it is always very helpful for both optimizations of the analytical method and dose level. The pilot could be done only with a few animals and a few samples of blood.

Some useful tips related to single-dose PK you can find in my paper below:

Article Comparison of bioequivalence study regulatory requirements f...

Best regards

Tomasz

Dear Shubham Arunrao Chinchulkar,

The contributions of Sonia Gera are more than enough to inform the discussion. the dose of animal totally depends on LD50 value and route of administration.

1. if you load a drug in any carrier system then first you find the % release of the drug and LD50. Then after you calculated based on body weight (totally depends on release kinetics).

2. if you directly give drugs or synthetic compounds. you should first find the LD50 of the compound and then calculate it on the basis of body weight.

good luck!