Plasma half-life — the time required for the plasma concentration of a compound to fall to half its peak value — is one of the single most useful numbers for interpreting a peptide’s reference research-dosing schedule. This guide describes how research protocols use half-life to derive frequency, and works examples across the range of half-lives common in the peptide reference literature.
The core relationship
For a compound that follows first-order pharmacokinetics — the pattern that describes most peptides in the research literature — the plasma concentration halves every t½ hours. Five half-lives cover approximately 97% of the elimination cycle: at 5·t½, plasma concentrations are 1/32 of the initial peak, generally treated as functionally cleared.
Two operational rules follow from that:
- To keep a compound present, administration must be more frequent than 5·t½. Beyond that spacing, plasma concentration falls into a trough where the compound is functionally absent between doses.
- To reach steady-state, at least 4–5·t½ of consistent dosing is required. Below that duration, plasma concentrations have not yet plateaued.
Half-life buckets in the peptide literature
Peptides in the reference research literature fall into four broad buckets by half-life:
Very short half-life (t½ ≤ 1 hour)
Examples: Selank, Semax, GHK-Cu, native Sermorelin.
For these peptides, plasma concentrations after a single dose fall to a functional trough within a few hours. Reference research protocols in this bucket typically describe multiple doses per day or a single, timed daily dose where the intent is a discrete pulse rather than sustained presence.
Example — Sermorelin: with a plasma half-life of roughly 10–15 minutes, reference protocols use a single nighttime dose because the intent is to trigger a discrete GH pulse that mimics the endogenous nighttime GHRH signal. Multi-per-day sermorelin is uncommon in the research literature.
Short half-life (t½ ~ 1–4 hours)
Examples: Ipamorelin, BPC-157, Hexarelin, PT-141.
Reference protocols for peptides in this bucket typically describe once- or twice-daily administration, with dose timing sometimes aligned to intended activity (as with the PT-141 pre-activity dose) or to endogenous circadian pulses (as with GH-secretagogue peptides administered at bedtime).
Intermediate half-life (t½ ~ 12–72 hours)
Examples: TB-500, CJC-1295 DAC, MOTS-c.
Reference protocols in this bucket typically describe two or three doses per week. The intent is sustained plasma presence between doses, which is possible for these peptides because trough concentrations do not fall to zero within a 3–4-day interval.
Long half-life (t½ ~ 100+ hours)
Examples: Semaglutide, Tirzepatide, Retatrutide.
Reference protocols in this bucket use once-weekly administration. The pharmacokinetics permit stable steady-state plasma concentrations at a weekly cadence, and the long half-life is the direct rationale for that cadence.
Steady-state and titration
Because reaching steady-state takes 4–5·t½, reference protocols for long-half-life peptides commonly describe a titration period during which the dose is increased on a per-week schedule and the plasma level tracks toward a new steady-state at each step. Trial protocols for tirzepatide and retatrutide, for example, use 4-week step-ups — long enough for steady-state to establish at each dose before the next escalation.
For very short-half-life peptides, steady-state is achieved within a single day of dosing and titration schedules are shorter or non-existent.
Trough matters — the case of a pulse
For some peptides, the trough is the point, not a problem. GH-secretagogue peptides such as ipamorelin and hexarelin are administered in a way that produces a discrete pulse of GH release; the intent is a sharp rise-and-fall on the GH curve, not a plateau. Administration frequency in these cases is chosen to preserve pulse structure — typically two or three doses per day, well separated — rather than to maintain steady-state.
Trough matters — the case of tolerance and receptor desensitisation
For other peptides, avoiding continuous receptor occupancy is described as important to prevent tachyphylaxis or receptor downregulation. Hexarelin is a documented example: repeated close dosing produces attenuated GH responses, and reported protocols space the doses accordingly.
Rule of thumb
For a first pass at reading a protocol:
- t½ ≤ 1 hour → multiple daily doses, or a single timed daily dose.
- t½ 1–4 hours → once- or twice-daily.
- t½ 12–72 hours → two or three times weekly.
- t½ ≥ 100 hours → once-weekly with 4-week titration steps.
If a reference protocol deviates from this pattern, the deviation is usually deliberate — a receptor-occupancy consideration, an intended trough, or a pulse-preservation motive — and the rationale is typically stated in the primary literature.
Reminder
Nothing in this guide constitutes medical advice or a recommendation to administer any peptide. This is a scientific-reference description of the pharmacokinetic reasoning described in the research literature. See our disclaimer.