About This Calculator

The Drug Dose Conversion (Animal ↔ Human, BSA Method) calculator is an essential tool for researchers and clinicians in translational medicine. It facilitates the conversion of drug dosages between different species based on Body Surface Area (BSA), a method recommended by the U.S. Food and Drug Administration (FDA) for estimating a Maximum Recommended Starting Dose (MRSD) for first-in-human clinical trials.

What This Calculator Does

This tool performs two primary functions based on established allometric scaling principles:

• Animal to Human Conversion: It calculates the Human Equivalent Dose (HED) in mg/kg from a known animal dose in mg/kg. This is crucial for planning the initial safe dosage for human trials based on preclinical animal study data.
• Human to Animal Conversion: It calculates the Animal Equivalent Dose (AED) in mg/kg from a known human dose in mg/kg. This is useful for designing animal studies to investigate the efficacy or toxicity of a drug at dosages equivalent to those used in humans.

When to Use It

This calculator is most valuable during the drug development process, particularly in the following scenarios:

• Preclinical to Clinical Transition: When you have determined a No-Observed-Adverse-Effect-Level (NOAEL) in an animal model and need to estimate a safe starting dose for Phase 1 human trials.
• Translational Research: For comparing drug exposures across species to better understand pharmacokinetics (PK) and pharmacodynamics (PD).
• Designing Animal Studies: To establish relevant dose levels in animal models that correspond to therapeutic doses in humans.

Inputs Explained

• Conversion Direction: Choose whether you are converting an animal dose to a human equivalent (HED) or a human dose to an animal equivalent (AED).
• Source Species: The species for which the dose is already known. This will be an animal for HED calculations or Human for AED calculations.
• Enter Dose (mg/kg): The known dosage of the drug in the source species, expressed in milligrams per kilogram of body weight.
• Target Species: The species for which you want to find the equivalent dose. This will be Human for HED calculations or an animal for AED calculations.

Results Explained

Upon calculation, the tool provides a comprehensive output:

• Equivalent Dose: The primary result, either HED or AED, displayed in mg/kg, rounded to three decimal places.
• Formula Used: The specific mathematical formula applied for the conversion.
• Values Used: A clear summary of the input dose and the Km factors for both the source and target species.
• Calculation Breakdown: The complete calculation showing how the input values were used in the formula to arrive at the final result.

Formula / Method

The calculator uses the Body Surface Area (BSA) normalization method, which relies on a species-specific "Km factor". The Km factor is the ratio of the average body weight (kg) to the BSA (m²) for that species. The FDA provides standardized Km factors for common lab animals and humans.

Human Equivalent Dose (HED) Formula:

HED (mg/kg) = Animal Dose (mg/kg) × (Animal Km / Human Km)

Animal Equivalent Dose (AED) Formula:

AED (mg/kg) = Human Dose (mg/kg) × (Human Km / Animal Km)

Step-by-Step Example

Let's calculate the HED for a drug with a NOAEL of 50 mg/kg in a Rat.

1. Select Conversion Direction: Choose "Animal Dose to Human Equivalent Dose (HED)".
2. Select Animal Species: Select "Rat".
3. Enter Animal Dose: Input "50" mg/kg.
4. Identify Km Factors: The tool uses the standard values: Rat Km = 6, Human Km = 37.
5. Apply the Formula:
   HED = 50 mg/kg × (6 / 37)
6. Calculate the Result:
   HED = 50 mg/kg × 0.162
HED = 8.108 mg/kg

The calculated Human Equivalent Dose is approximately 8.108 mg/kg.

Tips + Common Errors

• Check Units: Ensure your input dose is in mg/kg. The conversion method is only valid for doses expressed in this unit.
• Select the Correct Species: Double-check that you have selected the correct animal model. Different monkey species, for example, may have different Km factors in some guidelines, though this tool uses 12 for all listed monkey types as per the 2005 FDA guidance.
• Understand the Limitations: This method is an estimation. It does not account for species differences in drug absorption, distribution, metabolism, and excretion (ADME) or target receptor sensitivity.
• Don't Confuse with Weight-Based Scaling: Simple dose scaling based on body weight is generally inaccurate and not recommended for interspecies conversion. BSA scaling is the industry standard for initial estimates.

Frequently Asked Questions (FAQs)

What is a Km factor?

The Km factor is a conversion constant used in allometric scaling. It represents the ratio of Body Weight to Body Surface Area (Weight/BSA) for a given species. It allows for the normalization of drug doses across species of different sizes.

Why is Body Surface Area (BSA) used for dose conversion instead of body weight?

Many physiological parameters, including metabolic rate, cardiac output, and blood flow, correlate more closely with BSA than with body weight across different species. Therefore, scaling doses by BSA provides a more accurate estimate of equivalent drug exposure.

Can I use this calculator to convert doses between two different animal species?

While the calculator is primarily designed for animal-human conversions, the underlying principle is the same. To convert between two animal species (e.g., Mouse to Rat), you would use the formula: Dose(Rat) = Dose(Mouse) × (Km(Mouse) / Km(Rat)). The calculator does not directly support this in its UI, which is fixed to human-centric conversions.

Is this BSA method applicable to all types of drugs?

The BSA method is a general guideline and is most applicable for cytotoxic anticancer agents and many small molecule drugs. It may be less accurate for biologics (like monoclonal antibodies), gene therapies, or vaccines, which may require different scaling approaches (e.g., scaling by weight or no scaling at all). Always consult specific FDA guidance for the therapeutic class.

Where do the Km factors in this calculator come from?

The Km factors are sourced directly from the U.S. FDA's "Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers" published in July 2005.

What is the difference between HED and the final clinical dose?

The HED is an estimated starting point for a Phase 1 clinical trial. The final therapeutic dose for humans is determined through extensive clinical trials (Phase 1, 2, and 3) that evaluate safety, tolerability, pharmacokinetics, and efficacy in human subjects.

What if my animal species is not listed?

If your species is not listed, you would need to find a scientifically validated Km factor for that species from literature or regulatory guidance. This calculator is limited to the species provided in the FDA's 2005 guidance document.

Does the 60 kg human body weight assumption affect the calculation?

No, the Km factor (37 for humans) already incorporates the standard 60 kg body weight assumption. The final HED is given in mg/kg, so it can be applied to a human of any weight to find the total dose (e.g., for a 70 kg person, total dose = HED in mg/kg × 70 kg).

References

1. U.S. Food and Drug Administration. (2005). Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. www.fda.gov
2. Reagan-Shaw, S., Nihal, M., & Ahmad, N. (2008). Dose translation from animal to human studies revisited. The FASEB Journal, 22(3), 659–661. faseb.onlinelibrary.wiley.com
3. Nair, A. B., & Jacob, S. (2016). A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy, 7(2), 27–31. www.ncbi.nlm.nih.gov
4. Shin, J. W., Seol, I. C., & Son, C. G. (2010). Interpretation of animal dose and its application to patients dose from preclinical study. Journal of Korean oriental medicine, 31(3), 1-8.