Yes, you can, the only thing you must know is the molecular weight of the substance (or substances) you are using and the volume of the diluent you are going to employ in the in vitro experiment. That way you can calculate the exact quantity of such substance (in mg, ug etc..) and establish a correlation between in vivo dosage and in vitro treatment. However, for in vitro treatments the employed amount of substance is usually much lower than in vivo.

Diego, can you provide a concrete example on what you are suggesting. Will appreciate it much.

Rob, your input is very much appreciated.

Thanks for the input dominic. I appreciate it.

Sure.

Imagine that the substance you are using is for example, NaCl. Its molecular weight (or molecular mass) is 58.453 g/mol (23 for the Na + 35.453 for the Cl). Using that 3 mg/kg dosage you propose, means that if you have an animal that weights 1 kg (maybe a very big rat, hehe) you must inject/gavage it with 3 mg of NaCl (Regardless the volume of diluent you want to use to administer those 3 mg).

If you want to know, what is the concentration you need to get those 3 mg of NaCl in your in vitro experiment, you only have to use the molarity formula (M = m/MW * 1/V where m = mass in grams, m = molecular weight of the substance and V = volume of the diluent in litres).

Assuming that you want to prepare 10 mL (V) of such substance for your in vitro experiments and knowing that MW of NaCL = 58.453 g/mol and m = 0.003 g. The resultant concentration (molarity) will be: 0.00000513 molar = 5.13 micro molar

But this is only the mathematical calculations, as Rob said, you can’t assume the same amount of substance for in vivo that for in vitro assays. For example, oral gavaging a rat with 3 mg of substance is not the same as treating an in vitro epithelium of intestinal cells growing over 1.1 cm2 diameter wells. Those 3 mg of substance will probably be very harzadous for the cells (Assuming your substance is harzadous). You must establish the quantity empirically by testing different amount of substance treatments on your cells.

Hello! There is no correlation between in vivo and in vitro doses. The only way to find a correct concentration for a specific in vitro study is a time-dependent dose-response curve. For example, some pharmacological inhibitors may act within 30-60 min, they might be reversible or not etc. There are a lot variations that can be eliminated by dose-response curves. Each in vitro model has its own particularity given by cell type, culture conditions, objectives etc.

Without the help of pharmacokinetic, you may use a dose-dependent curve (1,10,100,1000) to start, and once undertstood the range of efficacy you can refine better. IV treatment require less drug and, initially, by this way of treatment, to have an idea of how much drug to start your dose-dependent curve, you may consider the animal being as a test tube. In IV treatment your drug has to be clearly dissolved. If your drug acts mainly in the liver use only oral administrations

Thanks everyone for the valuable inputs.

In my view, there is no correlation in dose of in-vivo and in-vitro treatments and we can not extrapolate the dose from each other's dose. Both are different. As all knows in-vitro is a preliminary research to get the property of test compounds and of-course some extent pharmacodynamics. In in-vitro we work on a single or isolated cell; whereas in in-vivo with different tissues which interacts with each others physiology always. So, we can not convert either dose.

The wide range of efficacy dose selection can be done after cytotoxicity (in-vitro) and rodent toxicity study (in-vivo) by following some guidelines. By doing PK studies and PD studies in rodents we come to a fixed efficacy dose. Both research has different profile (even though same target). Finding a suitable dose in in-vitro or in-vivo is a systematic and long individual procedure. So, we can not convert either dose.

Is there's a way of finding a suitable concentration or conversion of an in-vivo dose of say 250 mg/kg of potassium oxonate or oxonic acid in mouse to be used in in-vivo dose in zebrafish? Can we then establish a correlation between the the zebrafish and mice based on that dose or concentration?

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!