PT-141 (Bremelanotide)

bremelanotide: drug concentration in plasma (ng/mL).

Published bremelanotide model at a fixed adult study profile.

Fixed reference profile: Fixed 74.5 kg premenopausal woman with HSDD; eGFR 95.22 mL/min/1.73m². Vyleesi bremelanotide acetate solution/autoinjector; Subcutaneous abdomen. Fixed reference weight: 74.5 kg.

Changing dose or schedule explores a scenario; it does not personalize the reference profile or establish a studied regimen.

Input dose basis: Milligrams of bremelanotide active free-base equivalent, as labeled; not acetate salt mass or syringe volume.

Source exposure scope: The fixed source model supports concentration simulation; changing dose or schedule is linear model extrapolation.

Vyleesi fixed study model

bremelanotide-fda-2019-model-157 · version 1

• Fixed premenopausal HSDD reference: 74.5 kg, eGFR 95.22 mL/min/1.73 m²; no individual random effects.
• FDA population-PK narrative calls CL/F and V2/F apparent, with model F1 fixed to1. Do not apply an additional bioavailability multiplier; F1 is a fitting convention, not a new absolute-F measurement.
• Concentrations are bremelanotide parent; no metabolite or pharmacodynamic response is modeled.

Model structure

Two compartments with absorption

Apparent clearance (CL/F)

7.11 L/hour

Apparent central volume (Vc/F)

2.19 L

Absorption rate (ka)

0.535 /hour

Apparent intercompartmental clearance (Q/F)

2.02 L/hour

Apparent peripheral volume (Vp/F)

6.04 L

Input mass conversion

1 mg modelled mass per mg entered

• The reference HSDD profile is not the healthy crossover cohort behind the label arithmetic means; do not claim exact reproduction of its 72.8/276 means.
• No endogenous mediator, libido response or personal effect is predicted.
• Dose-linear superposition is the model assumption; the label documents nonlinearity across 0.3–10 mg. Keep the studied product and exposure range explicit.
• Not clinical validation; table transcription and independent numerical reproduction only.
• Independent source check: despite table shorthand CL and V, the population-PK narrative explicitly describes apparent CL/F and V2/F. Use apparent parameter metadata; numerical values do not change.
• The label Cmax of 72.8 ng/mL and AUC of 276 ng·h/mL describe a different healthy-woman crossover cohort. This HSDD reference model is not normalized to those values.

• FDA Vyleesi review — accessible mirrored copy

  Mirrors the original FDA NDA 210557 review. FDA authored the review; this independent host is not FDA. Model 157, Table 3, printed page 48 (PDF page 293).

• FDA Vyleesi NDA 210557 multidisciplinary review, clinical pharmacology appendix model 157, Table 3, printed page 48

  Source-defined CL 7.11 L/h, central V2 2.19 L, peripheral V3 6.04 L, Q 2.02 L/h, Ka 0.535/h, F fixed 1. Reference covariates: 74.5 kg, eGFR 95.22 mL/min/1.73m², HSDD population, abdominal SC injection. Population analysis: 4632 plasma samples/963 premenopausal women across five phase I–III trials.

• VYLEESI label sections 11 and 12.3

  Single-dose product context: 1.75 mg bremelanotide/0.3 mL acetate formulation, SC; mean plasma peak 72.8 ng/mL, median Tmax 1 h, mean AUC 276 ng·h/mL, terminal half-life 2.7 h. Molecular weight 1025.2 free base. Broad dose range is less than proportional; high doses plateau.

• FDA review, clinical BA/BE assessment PT-141-56, printed pages 6–8

  The 72.8 peak/276 AUC study used 36 healthy women, BMI 18–32, crossover 1.75 mg SC prefilled syringe versus autoinjector, single doses separated by 48 h. LC-MS/MS plasma assay. Relative proportionality supported from 1 to 1.75 mg in this study.