As given earlier, the clinical dosage of doxorubicin for adults is 40-60 mg/m2 IV every 21-28 days. I want to conduct experiments with the anti cancer drug and would like to use concentrations that are clinically relevant. For that purpose, I want to know the conversion to mg/ml for the drug which is easier fr me to work with that mg/m2.
Miss Padmaja anand : You have the concentration of drug in terms of mg/m2. So, first find out the BSA or the average BSA of your animals using standard correlations(Search on the net u can find). Then multiply the given concentration with the BSA value. You will get the total amount of drug or dosage in 'mg'.Suitably dissolve your drug in required volume.I hope u know the conversion from mg/ml into molarity.Hope it is useful to u.
You may consider to use the cmax values from patients treated with “localized“ treatment like chemoembolization as a benchmark for the highest concentration used in patients.
Examples:
mean Cmax 1,928 ± 560.8 ng/ml, from van Malenstein H et al.: A randomized phase II study of drug-eluting beads versus transarterial chemoembolization for unresectable hepatocellular carcinoma. Onkologie. 2011;34(7):368-76.
mean Cmax 2341.5+/-3951.9 ng/mL, from Varela M et al.: Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007 Mar;46(3):474-81.
It may be of interest that doxorubicin is clinically used in much higher concentrations for INTRAVESICAL applications: here concentrations up to 1 mg/ml (no typo: 1 mg/ml) are used and remain in the urinary bladder (without much dilution by urine) for 1 hour.
The concentration of Doxorubicin is mentioned for square metre. i.e 40 to 60 mg for sq meter (of humans). If you going to use the same drug in murine models....there will be lot of literature for the dosage. Pls go through it. Find the relevance of surface area of your murine model with human and then calculate the dose according to it.
There are two conversions to perform. I think you should first convert the dose in Body surface area (BSA) in humans to body weight dose. ie: 3700 mg/sq.m (3700/37) is equivalent to 100 mg/kg for humans. Divide this value by 12 (the conversion factor from humans to mice) that is 100/12. this will give you the body weight dose corresponding to mice=8.33 mg/kg. Freireich, EJ, et al. Quantitative comparison of toxicity of anticancer agents in mouse,
rat, dog, monkey and man. Cancer Chemother Rep.1966;50(4):219-244.
Hi everyone, thanks to Ashif Iqubal, I have located the 1966 paper, however I have more questions after reading this paper. I am going to share some content from this paper since it isn't available online, and you can only get the physical printed copy from certain libraries.
In the summary of the paper, it stated that: " The best estimate of the MTD (maximum tolerated dose) in man is made by weighting the estimates from the various animal species. Dose on an mg/m^2 basis is approximately related to dose on an mg/kg basis by the formula:
(dose in mg/m^2) = (km)i x (dose in mg/kg), (i=1,...,7)
where (km)i is the appropriate factor for converting doses from mg/kg to mg/m^2 surface area for each species."
Here, they mentioned that "On an mg/kg basis, the MTD in man is about 1/12 the LD10 in mice, 1/9 the LD10 in hamster...etc"
Do note that the conversion factor of 12, for human to mice, used here, is based on MTD.
Then, under the Appendix II (Page 238) and table I (Page 240), "Relationship between drug doses in milligram per kilogram and milligram per square meter of surface area for man and for small and large animals", It seems to suggest the (km), conversion factor for mice weighing 20g (0.02 kg), is = 3.0. In the table, there's a breakdown of the murine conversion factor (km), ranging from 2.9 to 3.2; based on their body weight (kg).
Therefore, my question is, should we be using km =3 or km=12 for this matter?