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Allometric Dose Scaling.

Convert mouse, rat, and human doses using the Reagan-Shaw et al. (2008) FASEB J body-surface-area method. Computes human equivalent doses (HED) with canonical Km factors and cross-species comparison tables.

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Validated2026-04-06
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Load example allometric dose scaling calculator data to see the full workflow

Source & Target

Defaults: mouse 25 g, rat 250 g, human 70000 g.

Equivalent Dose

Allometric scaling is a starting point only. Verify with PK data; do not use for drugs with non-linear pharmacokinetics.
Target dose
8.11 mg/kg
human from mouse
Scaling factor
0.081
Km_src ÷ Km_tgt
Method
Reagan-Shaw
FASEB J. 2008

Cross-Species Comparison

SpeciesWeightBSAmg/kgTotal dose
mouse25 g0.0083100.002.500 mg
rat250 g0.041750.0012.500 mg
human70000 g1.89198.11567.568 mg

When to use

  • Estimating a human equivalent dose (HED) from rodent efficacy data
  • Converting between mouse and rat doses for cross-species replication
  • Sanity-checking a published animal dose against a human trial dose
  • Building a first-in-human starting dose for FDA IND submissions
  • Justifying cross-species dose decisions in IACUC protocols

Do not use for

  • For drugs with documented non-linear or saturable pharmacokinetics
  • For monoclonal antibodies and other biologics with target-mediated disposition
  • For final clinical trial dose selection without empirical PK data
  • For species outside {mouse, rat, human} — use the full Reagan-Shaw Km table instead

Mouse → human is divide by ~12.3, not 1

A 100 mg/kg mouse dose is NOT a 100 mg/kg human dose. The BSA correction gives ~8.1 mg/kg HED. Skipping this step is a common reason early human trials see unexpected toxicity.

Rat → human is divide by ~6.2

Rats are larger and have a higher Km (6 vs 3 for mouse), so the correction is less aggressive. A 50 mg/kg rat dose translates to ~8.1 mg/kg HED — coincidentally the same as a 100 mg/kg mouse dose.

BSA scaling assumes linear PK

The method works when drug clearance is proportional to BSA across species. For drugs with saturable metabolism, target-mediated disposition, or species-specific metabolism, BSA scaling can be off by 10× or more.

Use the calculator as a starting point, not a final dose

The FDA Guidance recommends BSA scaling as the *starting* point for the maximum recommended starting dose (MRSD). The actual MRSD is then divided by a 10× safety factor. This calculator gives you the BSA-scaled HED — apply your own safety factor for clinical use.

1

Method

BSA (m2\text{m}^{2}) = body_weight_kg / Km_species, where Km is the canonical Reagan-Shaw factor (mouse 3, rat 6, human 37). HED (mg/kg) = animal_dose ×\times (Km_animal / Km_human). The calculator generalizes this to any source/target pair in {mouse, rat, human} via Dose_target = Dose_source ×\times (Km_source / Km_target).

2

Validated

Last validated 2026-04-06. Calculations are designed for planning and documentation support; verify procurement decisions against manufacturer specifications or institutional SOPs.

3

How to cite

How to Cite

ConductScience Allometric Dose Scaling Calculator (v0.88.0). ConductScience, Inc. 2026. Available at: https://conductscience.com/tools/allometric-dose-scaling-calculator

Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22(3):659-661.

Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27-31.

U.S. Food and Drug Administration. Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. CDER; 2005.

The Reagan-Shaw Method

Reagan-Shaw, Nihal & Ahmad (2008) revisited the FDA Guidance for Industry on Estimating the Maximum Safe Starting Dose in clinical trials. The core insight is that drug clearance scales with body surface area, not body weight, across species.

The Km factor

For each species, Km = body_weight_kg / body_surface_area_m². This ratio is approximately constant within a species and reflects the fact that smaller animals have a much larger surface-to-volume ratio than larger animals.

Canonical Km values (Reagan-Shaw Table 1)
  • Mouse: Km = 3
  • Hamster: Km = 5
  • Rat: Km = 6
  • Guinea pig: Km = 8
  • Rabbit: Km = 12
  • Cat: Km = 12
  • Monkey: Km = 12
  • Dog: Km = 20
  • Human (adult, 60 kg): Km = 37
The conversion

HED (mg/kg) = animal_dose (mg/kg) ×\times (animal_Km / human_Km).

For mouse → human: HED = mouse_dose ×\times (3/37) \approx mouse_dose ×\times 0.081. For rat → human: HED = rat_dose ×\times (6/37) \approx rat_dose ×\times 0.162.

This calculator generalizes the formula to any pair of species in {mouse, rat, human}.

When BSA Scaling Falls Apart

BSA scaling is a *starting point*, not a substitute for proper pharmacokinetic modeling. Conditions under which the method underestimates or overestimates the true HED:

Non-linear pharmacokinetics

Drugs cleared by saturable enzymes (e.g. high-affinity CYP3A substrates near Vmax) do not scale linearly with BSA. The mouse may clear the drug efficiently while the human is enzyme-saturated at the BSA-equivalent dose.

Target-mediated drug disposition (TMDD)

For monoclonal antibodies and other biologics, clearance is dominated by target binding and internalization. BSA scaling does not capture this — use receptor occupancy modeling instead.

Species-specific metabolism

Some CYP isoforms (CYP2D6, CYP2C19) have very different activity profiles between rodents and humans. A drug that is 90% cleared by CYP2D6 in humans may be cleared by an unrelated isoform in mice.

Active metabolites

If the parent compound is a prodrug, BSA scaling on the parent dose can dramatically misestimate the active metabolite exposure. Always verify with PK data when active metabolites are involved.

Practical guidance

Use BSA scaling for: (1) initial cohort sizing, (2) IACUC dose justification, (3) sanity-checking published doses, (4) FDA IND HED estimation per the 2005 Guidance for Industry. Do NOT use it as the final dose for a clinical trial without empirical PK data.

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