Also known as: bremelanotide · Vyleesi · PT141
| Parameter | Value | Source |
|---|---|---|
| Elimination Half-Life (SC) | ~2.7 hours | FDA NDA 210557; Clayton AH et al. PMID 26944463 |
| Tmax (SC) | ~1 hour | FDA NDA 210557 |
| Route(s) of Administration | Subcutaneous autoinjector (abdomen or thigh) | — |
| Plasma Protein Binding | ~21% | FDA NDA 210557 |
| Time to Steady State | N/A — PRN dosing (not daily use) | — |
| Accumulation at Steady State | Minimal (PRN use; max 1 dose per 24 h) | — |
| Full Clearance (5 half-lives) | ~13.5 hours | Calculated from NDA 210557 t½ |
| Standard Dosing Frequency | 1.75 mg SC PRN ≥45 min before activity; max 1 per 24 h | FDA NDA 210557 |
| Data Quality | Human RCT — FDA NDA 210557; Clayton AH et al. J Sex Med 2016 PMID 26944463 | |
PT-141 (bremelanotide, trade name Vyleesi) has an elimination half-life of approximately 2.7 hours after subcutaneous injection, based on FDA NDA 210557 pharmacokinetic data and human RCT evidence.[1][2] With a Tmax of approximately 1 hour, peak plasma concentrations are reached within the first hour, and the compound is substantially cleared from plasma (~97%) within approximately 13.5 hours of dosing. This PK profile supports the approved PRN (as-needed) dosing paradigm.
Bremelanotide is a synthetic cyclic hepta-peptide derived from Melanotan II, approved by the FDA in June 2019 under NDA 210557 for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women.[1]
The PK data in FDA NDA 210557 characterizes the plasma concentration-time profile after a single 1.75 mg SC dose. The terminal elimination half-life of ~2.7 hours is derived from population PK modeling and single-dose PK studies. The Clayton et al. (2016) Phase 2 dose-finding RCT confirmed the ~2.7-hour half-life at the 1.75 mg dose used in Phase 3 trials.[2]
PT-141's ~2.7-hour plasma half-life is shorter than its observed clinical effect duration of approximately 6–12 hours for pro-sexual desire effects. Once MC4R signaling cascades are activated in hypothalamic nuclei (medial preoptic area), the downstream neural circuits mediating sexual motivation continue to operate at plasma concentrations below the peak. The clinical instruction to inject ≥45 minutes before activity reflects the Tmax (~1 hour) — onset of peak CNS exposure — not the end of the effect window.[1][3]
After a single 1.75 mg subcutaneous dose, PT-141 plasma concentrations decline with a t½ of ~2.7 hours. Full clearance occurs within approximately 13.5 hours.
| Half-Lives Elapsed | Time After Dose | % Remaining in Plasma | Clinical Note |
|---|---|---|---|
| 1 | ~2.7 hours | 50% | Within peak effect window (Tmax ~1 h) |
| 2 | ~5.4 hours | 25% | Clinical effects typically ongoing |
| 3 | ~8.1 hours | 12.5% | Effects beginning to taper |
| 4 | ~10.8 hours | 6.25% | Near-complete plasma clearance |
| 5 (clinical clearance threshold) | ~13.5 hours | ~3% | Pharmacologically negligible; consistent with max 1 per 24 h limit |
PT-141's ~2.7-hour half-life and ~13.5-hour full clearance period are suited to PRN dosing. The compound reaches peak plasma concentration within ~1 hour, produces effects lasting approximately 6–12 hours, and is substantially cleared within 13–14 hours — compatible with situational pre-activity use. Daily dosing is not required because the MC4R mechanism does not require tonic receptor occupancy; acute activation is sufficient to produce the desired neural effect.[1]
PT-141 is PRN rather than scheduled, so the concept of a missed dose does not apply pharmacokinetically. There is no trough-maintenance requirement and no accumulation effect under the approved once-per-24-hour maximum. Each dose is pharmacologically independent.
| Compound | Half-Life | Dosing | Mechanism | Status |
|---|---|---|---|---|
| PT-141 (Bremelanotide / Vyleesi) | ~2.7 h (SC) | PRN ≥45 min before activity | MC4R agonist (CNS hypothalamus) | FDA-approved NDA 210557 |
| Flibanserin (Addyi) | ~11 h (oral) | 100 mg oral once daily at bedtime | 5-HT1A agonist / 5-HT2A antagonist | FDA-approved NDA 022526 |
| Oxytocin (intranasal) | ~30 min (intranasal) | PRN intranasal before activity | Oxytocin receptor (CNS) | Not FDA-approved in US for sexual function |
| Route | Half-Life | Notes |
|---|---|---|
| Subcutaneous (abdomen, thigh) | ~2.7 hours | Only approved route; NDA 210557 data. Well-absorbed. |
| Intranasal (historical) | Shorter than SC (estimated); no current clinical data | Earlier development candidate; not the approved route or current formulation. |
| Intravenous | Shorter (no published clinical data) | Not a clinical or approved route. |
| Oral | Not viable | Proteolytic GI degradation of cyclic peptide; not a viable route. |
Bremelanotide (Vyleesi) is FDA-approved and not included in standard WADA or workplace drug screening immunoassay panels. It is not classified as a substance of abuse and is not screened by routine panels.
Specialized LC-MS/MS can detect bremelanotide and its primary metabolite (des-cyclo tetrapeptide fragment) in plasma and urine. Given the ~2.7-hour plasma half-life and full clearance within ~13.5 hours, urine detection using specialized methods would be expected to be limited to approximately 12–24 hours after the last dose. No published forensic urinary detection window study specific to standard panel immunoassay for Vyleesi has been identified.
Bremelanotide is a synthetic cyclic hepta-peptide (Ac-Nle-cyclo[Asp-His-d-Phe-Arg-Trp-Lys]-OH, molecular weight ~1,025 Da). The cyclic ring structure provides substantially greater proteolytic resistance than linear peptides of similar size — the ring conformation limits protease access to peptide bonds.[1] This metabolic stability extends the half-life from the seconds-to-minutes of native α-MSH to approximately 2.7 hours.
Despite the cyclic structure, bremelanotide is still cleared by hepatic metabolism and renal excretion of metabolite fragments. Plasma protein binding is approximately 21% — low, meaning the unbound fraction available for clearance is high. The absence of albumin-binding side chains or FcRn-recycling mechanisms limits the half-life to the ~2.7-hour range rather than extending it to days.[1]
Melanocortin receptor selectivity: bremelanotide binds MC1R, MC3R, MC4R, and MC5R. The pro-sexual desire effect is attributed primarily to MC4R agonism in the medial hypothalamus. MC1R activation contributes to transient skin flushing; off-target MC3R/MC5R activation contributes to nausea — the most common adverse effect in clinical trials.[3]
Log PT-141 dose and injection time. Halflife models your plasma concentration curve based on the ~2.7-hour half-life, showing exactly when you are in the peak-effect window. On-device, no account required.
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