what rapamycin intake in humans (in grams per day) equals to the rapamycin intake seen in ITP mice (42ppm rapamycin)
ChatGPT
Rapamycin Dosage Comparison: Humans vs. Mice
Thought for 2m 8s
Short Answer:
Roughly 40 milligrams (0.04 grams) of rapamycin per day in a 70 kg human would produce a body-surface-area-adjusted exposure similar to the 42 ppm dosing regimen used in the ITP mice.
Detailed Explanation and Calculation Steps:
Understanding the Mouse Dose at 42 ppm:
42 ppm means that there are 42 milligrams of rapamycin per kilogram of mouse feed. Mice typically eat enough chow daily so that 42 ppm rapamycin in the diet corresponds to approximately 7 mg of rapamycin per kilogram of mouse body weight per day. This figure arises from data and scaling performed in previous studies by the National Institute on Aging’s Interventions Testing Program (ITP).
Converting Mouse Dose to a Human Equivalent Dose (HED):
To translate an animal dose to a human equivalent, we use allometric scaling based on body surface area (BSA), since metabolism and drug clearance rates do not scale linearly with body weight alone.
The commonly used formula is:
HED (mg/kg)
Animal dose (mg/kg)
×
Animal Km
Human Km
HED (mg/kg)=Animal dose (mg/kg)×
Human Km
Animal Km
Km values:
Mouse Km ≈ 3
Human Km ≈ 37
Apply the formula:
Given the mouse dose is about 7 mg/kg/day:
HED (mg/kg)
7
mg/kg/day
×
3
37
≈
7
×
0.081
≈
0.567
mg/kg/day
HED (mg/kg)=7mg/kg/day×
37
3
≈7×0.081≈0.567mg/kg/day
Scaling to an Average Adult Human Weight: Assume a human body weight of 70 kg:
Daily human dose
0.567
mg/kg/day
×
70
kg
≈
39.7
mg/day
≈
40
mg/day
Daily human dose=0.567mg/kg/day×70kg≈39.7mg/day≈40mg/day
40 mg/day = 0.04 g/day.
Conclusion: If we match the body-surface-area-adjusted exposure, a 70 kg human would need to take on the order of 40 mg/day (0.04 grams/day) of rapamycin to approximate the dosing regimen (42 ppm) used in the ITP mouse studies.