Rapamycin (Sirolimus) — Research Protocol
⚠️ RESEARCH SUMMARY — NOT A TREATMENT PROTOCOL. Discuss all findings with your healthcare provider.
Published research on rapamycin has investigated low-dose, intermittent regimens to achieve mTORC1 inhibition while sparing mTORC2 and immune function. Dosing regimens in published literature vary significantly from immunosuppressive transplant doses. This page summarizes published research protocols. It is not a guide for self-treatment. Discuss any treatment decisions with your physician.
Research Dosing (from Published Studies)
| Context | Dose | Route | Frequency | Notes |
|---|---|---|---|---|
| Longevity research | Dosing regimens in published literature vary — consult the cited studies for details | Oral | Intermittent (see cited trial) | PEARL trial investigated intermittent regimens. Published studies have investigated various dosing approaches to minimize immunosuppression while achieving pulsatile mTORC1 inhibition. |
| Anti-cancer (FDA-approved everolimus) | Dosing regimens in published literature vary — consult the cited studies for details | Oral | See cited trial | Everolimus (rapalog) studied for renal cell carcinoma. Published studies have investigated various dosing approaches for sustained anti-tumor effect. |
| Preclinical aging (mouse models) | 14 ppm in diet (mouse model) | Oral (mouse) | Continuous | ITP (Interventions Testing Program) preclinical protocol. 14% median lifespan extension reported in male mice, 9% in females. Animal data; not directly applicable to humans. |
Pharmacokinetics
Oral bioavailability ~15-20%. Half-life 57-63 hours (allows weekly dosing). CYP3A4 substrate — grapefruit juice increases levels 3.5x. Steady-state trough levels for longevity protocols target 3-8 ng/mL (vs 8-20 ng/mL for transplant immunosuppression).
Safety Profile
At longevity doses: generally well tolerated. Common: mouth sores (stomatitis, ~25%), mild lipid elevation. Uncommon: delayed wound healing, mild leukopenia. At immunosuppressive doses: increased infection risk, hyperlipidemia, thrombocytopenia, proteinuria.
Contraindications
- Active infection
- Immunocompromised state
- Within 2 weeks of surgery or planned surgery
- Severe hepatic impairment
- Pregnancy or breastfeeding
- Hypersensitivity to sirolimus
Monitoring Parameters
- Complete blood count (monthly initially)
- Fasting lipid panel (baseline, 3-month, 6-month)
- Fasting glucose/HbA1c (quarterly)
- Liver function tests (baseline, then periodic)
- Oral mucosa inspection for stomatitis