4.5.2 Human-to-Animal Dose Conversion

Because metabolic rate does not scale linearly with body weight, a simple per-kilogram conversion of a human dose to an animal dose is scientifically...

Because metabolic rate does not scale linearly with body weight, a simple per-kilogram conversion of a human dose to an animal dose is scientifically invalid. The Body Surface Area (BSA) method, recommended in the FDA's 2005 Guidance for Industry on estimating the maximum safe starting dose in initial clinical trials, instead scales dose according to the ratio of species-specific Km factors: Animal dose (mg/kg) = Human dose (mg/kg) × (Human Km ÷ Animal Km). Km factors are approximately 37 for humans, 6 for rats, 3 for mice, 12 for rabbits, 20 for dogs, and 12 for monkeys. As a worked example, a human dose of 10 mg/kg converts to an approximate rat dose of 10 × (37/6) ≈ 61.7 mg/kg. An alternative approach, allometric scaling, uses body weight raised to the power 0.75 to account for the non-linear relationship between body size and metabolic rate across species.