CalcDose for drug dosage conversions
It is commonly observed that small animals have to be administered large dosages (per kilogram body weight) as compared to big animals or humans to achieve similar pharmacological effects. For instance, about five-fold higher dosages of prednisolone and caffeine have been reported for rats as compared to humans. These variations occur due to varying metabolic activities of different animals. Although body weight varies from animal to animal across and within species, there is a remarkable consistency of the daily expenditure of energy expressed per metabolically active mass (MAM). About 20-30% of the whole body mass constitute fat material, which is metabolically inactive. On the other hand, the lean body mass (about 75% of body weight) contains all the body protein which takes part in maintaining homeostasis and is metabolically active. MAM is equal to body weight raised to 0.75 power, and holds true for freely feeding animals of different species as well as animals within a species. Although, in most of the pharmacological studies, the dosage of a drug is usually expressed in terms of milligram per kilogram (mg/kg) body weight, few investigators have also used less common but more realistic terms like mg/kg MAM or mg/m2 body surface area (BSA).
Figure 1. Comparative view of dose conversion using actual body weight (BW) and metabolically active mass (MAM) of animals. Reported human dosages for 8 drugs were used to calculate appropriate dosages for rats. The shaded areas indicate the percent variations from the reported dosages while using BW (light shaded) or MAM (dark shaded) procedures. CalcDose program was used for MAM procedure.
Pharmacologists often face the problem of finding an optimum reference dosage to start with, for their initial pilot studies. A suitable dosage conversion has to be performed, if the dosage of a drug for the same species is unknown but for a totally different species is known to experimenter. There are two important methods for dosage conversions, based on BSA or MAM calculations, and provide a more accurate cross-species comparison of activity and toxicity of various drugs. Several BSA based programs are accessible online for drug dosage conversions. These programs are suitable for human studies only, as one of the input parameters is height, which is difficult to measure in case of small animals and perhaps there is no established criteria for this purpose. Our Software, CalcDose has been designed for dosage conversions between animals and humans, and is based on MAM measurements .
Figrue 2. Input window: showing entries for the calculation of a human equivalent dose using the known animal dosage.
Figure 3. Report window: showing a representative print-out of results.
CalcDose software can be effectively used to calculate human equivalent dose of a drug tested in experimental animal. The main features of the program are optimal simplicity and flexibility of data input and a comprehensive report format. In pharmacological studies, body weight of experimental animals is exclusively expressed in grams or kilograms which can be directly selected using the option buttons on the input form rendering the program more time-efficient. The results output window not only shows the intended dose calculation, instead comprised of the body weight of both the animals and their respective mg/kg and actual doses. Thus, if any doubt or discrepancy is impended in results, the user can countercheck the data entry by viewing the report itself.
Khan HA (2003) CalcDose: A software for drug dosage conversion using metabolically active mass of animals. Drug. Chem. Toxicol. 26 (1), 53-60.