The bioavailability and blood levels of low-dose rapamycin for longevity in real-world cohorts of normative aging individuals.

Rapamycin, also known as sirolimus, has demonstrated great potential for application in longevity medicine. However, the dynamics of low-dose rapamycin bioavailability, and any differences in bioavailability for different formulations (e.g., compounded or commercial), remain poorly understood. We thus explored rapamycin bioavailability in two real-world cohorts to begin providing a foundational understanding of differences in effects between formulations over time. The small trial study cohort was utilized to explore the blood rapamycin levels of commercial (n = 44, dosages 2, 3, 6, or 8 mg) or compounded (n = 23, dosages 5, 10, or 15 mg) rapamycin 24 h after dose self-administration. Results suggested dose-to-blood level relationships were linear for both formulations, though compounded had a lower bioavailability per milligram of rapamycin (estimated to be 31.03% of the same dose of commercial). While substantial inter-individual heterogeneity in blood rapamycin levels was observed for both formulations, repeat tests for individuals over time demonstrated relative consistency. Extending exploration to 316 real-world longevity rapamycin users from the AgelessRx Observational Research Database produced similar findings, and additionally suggested that blood rapamycin levels peak after 2 days with gradual decline thereafter. Taken together, our findings suggest that individualized dosing and routine monitoring of blood rapamycin levels should be utilized to ensure optimal dosing and efficacy for healthy longevity.