I had a reviewers comments regarding calculation of drug dose from cell culture to mouse and then human equivalent dose. I did both in vitro and in vivo (mouse) experiments for specific single compounds isolated from bread crust. The question is: How can I calculate the equivalent dose for humans?
Thanks in advance everyone share your suggestions...
You can use MIRD method which stands for Medical internal radiation dosimetry.
You need to calculate the cumulative activity of each organ
see these papers
Article Estimated background doses of [67Ga]-DTPA-USPIO in normal Ba...
Article Assessment of effective absorbed dose of In-111-DTPA-Buserel...
Article Determination of human absorbed dose of 67GA-DTPA-ACTH based...
Article Estimation of human effective absorbed dose of 67Ga-cDTPA-go...
Hi Saeed Shanehsazzadeh,
Thanks for your updated information, the articles you attached is very useful to me calculate the equivalent dosage...
You must be quite prudent. In toxicology (drug safety) there are many units to establishing the safety use of drugs in humans. The concepts NOEL, ASDI, ADI are Safety factors that must be attended, taking in consideration the nature of the molecule (drug), the exposure assessment, via of administration. The "risk characterization" is calculated as functions of probabilities integrating the organic kinetic of the molecules (hazard identification), via of administration, doses and frequency of administration.
It's quite complicated to convert from in vitro to in vivo or vice versa. Many many modifications and ADME-properties can drastically change the activity of compound that you are testing. Still following methods can be used for an approximation of the drug dosages!
Say you`re working with a drug - DRUG X with clinical dosage of 100 mg/m2.
Method 1:
Clinical dosage of DRUG X is 100 mg/m2.
Assuming that we`re doing viability assay in 96 well plates. The surface area of a single well in 96 well plate is 0.32 cm2, which means that we will need the following equivalent in vitro dose in each well = 100*3.2e-5 = 0.0032 mg.
Now, in order to calculate the concentration of 0.0032 mg of DRUG X for in vitro experiment, we can use the molarity formula (M = m/MW * 1/V where m = mass in grams, MW = molecular weight of the substance and V = volume of the diluent in litres).
We need 0.0032 mg of DRUG X in 100 µL or 0.0001 L (V) for our in vitro experiments (96-well plate) and knowing that MW of DRUG X = 588.72 g/mol and m = 0.0000032 g.
The resultant concentration (molarity) will be: 0.00005435 M or 54.35 µM.
Method 2:
Clinical dosage of DRUG X is 100 mg/m2.
Mice dosage in mg/kg = Human Equivalent Dosage in mg/m2 / Mice Km = 100 / 3 = 33.3 mg/kg
Assuming that average mouse weight is 25 gms, amount of DRUG X administered to each mouse = (33.3/1000)*25 = 0.8325 mg
Now, in order to calculate the concentration of 0.8325 mg of DRUG X in our in vitro experiment, we can use the molarity formula (M = m/MW * 1/V where m = mass in grams, MW = molecular weight of the substance and V = volume of the diluent in litres).
Assuming that we would like to make 25 ml or 0.025 L (V) of DRUG X solution for our in vitro experiments (assumption is 25g mice as 25ml volume) and knowing that MW of DRUG X = 588.72 g/mol and m = 0.0008325 g.
The resultant concentration (molarity) will be: 0.00005656 M or 56.56 µM.
As mentioned earlier, these calculations are just approximations!
- Badges
- Science method