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Rapamycin (Sirolimus)

Longevityprescriptionoral · inferred

Macrolide mTOR (mTORC1) inhibitor originally approved as an immunosuppressant for renal transplant and later for lymphangioleiomyomatosis. Flagship off-label longevity compound: intermittent weekly dosing (typically 5-10 mg once weekly) is theorized to preferentially inhibit mTORC1 while sparing mTORC2, avoiding glucose intolerance and immunosuppression seen with daily use. Low oral bioavailability (~14%), extensively metabolized by CYP3A4 and a P-gp substrate, yielding many drug interactions. Grey-market use for healthspan/lifespan extension based on robust rodent longevity data.

Projected serum levels — 5 mg, weekly

Rapamycin (Sirolimus)
Rapamycin (Sirolimus) modeled serum levels, 5 mg weekly over 21 days Population-based pharmacokinetic estimate. Steady state reached after approximately 7 days. 0 0.25 0.50 0.75 1 Day 0 Day 5 Day 11 Day 16 Day 21 Time on a regular schedule ≈ steady state · day 7

Maintenance schedule: 5 mg weekly (oral).

Modeled steady state after ~7 days: peak ≈ 0.79 mg, trough ≈ 0.11 mg body load. Population-based estimate over 21 days for a 5 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Longevity
Route modeled
Oral
Model confidence
inferred
Half-life
2.6 days
Common dose
5 mg
Suggested maximum
10 mg/day
Reference dose range
2.5–10 mg (single dose)
Suggested cadence
weekly
Validated against
2 mg oral — Cmax 0.000 mg/L at 1.4 h

Documented interactions

  • contraindicated
    Efavirenz (Sustiva) + Rapamycin (Sirolimus) CYP induction

    Efavirenz (Sustiva) inducer of CYP3A4 predicted to change Rapamycin (Sirolimus) AUC by ~0.15x

  • contraindicated
    Rifampin + Rapamycin (Sirolimus) CYP induction

    Rifampin inducer of CYP3A4 predicted to change Rapamycin (Sirolimus) AUC by ~0.15x

  • danger
    7-Hydroxymitragynine (7-OH) + Rapamycin (Sirolimus) CYP inhibition

    Rapamycin (Sirolimus) reversible_inhibitor of CYP3A4 predicted to change 7-Hydroxymitragynine (7-OH) AUC by ~2.20x

  • danger
    Alfuzosin (Uroxatral) + Rapamycin (Sirolimus) CYP inhibition

    Rapamycin (Sirolimus) reversible_inhibitor of CYP3A4 predicted to change Alfuzosin (Uroxatral) AUC by ~3.33x

  • danger
    Alprazolam (Xanax) + Rapamycin (Sirolimus) CYP inhibition

    Rapamycin (Sirolimus) reversible_inhibitor of CYP3A4 predicted to change Alprazolam (Xanax) AUC by ~3.33x

  • danger
    Amlodipine (Norvasc) + Rapamycin (Sirolimus) CYP inhibition

    Amlodipine (Norvasc) reversible_inhibitor of CYP3A4 predicted to change Rapamycin (Sirolimus) AUC by ~2.36x

Serum checks 274 modeled interaction pairings for rapamycin (sirolimus) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. mTOR inhibition improves immune function in the elderly Mannick JB et al. · Science Translational Medicine, 2014 DOI

    Landmark RCT showing low-dose RAD001 (rapamycin analog) improved influenza vaccine response by ~20% in elderly adults, providing first human evidence that mTOR inhibition reverses age-related immune decline.

  2. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity Lamming DW et al. · Science, 2012 DOI

    Established that chronic rapamycin disrupts mTORC2 causing insulin resistance, while lifespan extension is mediated by mTORC1 inhibition, supporting the rationale for intermittent dosing protocols.

  3. Rapamycin, the only drug that has been consistently demonstrated to increase mammalian lifespan Kaeberlein M · Experimental Gerontology, 2013 DOI

    Review summarizing evidence that rapamycin extends lifespan in all tested model organisms including mice and discusses translation to human geroscience applications.

3 published studies referenced in the app, each with a plain-language summary.