LL-37 half-life & pharmacokinetics

Reported half-life

Highly context-dependent. Plasma half-life of exogenously administered LL-37 is estimated at approximately 30–60 minutes due to rapid protease inactivation (neutrophil elastase, trypsin, cathepsin D). Biological activity at wound sites may persist longer due to sequestration in extracellular matrix and binding to DNA and glycosaminoglycans.

The half-life and pharmacokinetic profile of LL-37 reported above is drawn from the published pre-clinical literature. Plasma half-life describes the time taken for the circulating concentration to fall by half after a single dose; tissue half-life — which may be longer for peptides retained in specific organs or matrices — is a distinct and often more relevant parameter for healing research, where the duration of exposure at the injury site matters more than the systemic exposure profile.

Routes of administration studied

• Topical
• Intradermal
• Subcutaneous (animal research)
• Intranasally (mucosal animal studies)

Different routes produce materially different pharmacokinetic profiles for the same peptide. Subcutaneous administration generally produces flatter, more sustained plasma profiles than intravenous bolus dosing; intraperitoneal administration (common in rodent models) is not directly translatable to human routes; oral administration faces the additional challenge of luminal and brush-border peptidase degradation, which is why most research peptides have very low oral bioavailability without protective formulation.

Drug class

Human cathelicidin antimicrobial peptide (CAMP); innate immune effector peptide

Mechanism context

Half-life interpretation depends on the underlying mechanism. LL-37 acts as follows:

LL-37 is the sole human representative of the cathelicidin family of antimicrobial peptides. The mature 37-amino-acid peptide (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) is cleaved from its 18 kDa precursor hCAP-18 by serine proteases including kallikrein 5 and 7 at skin surfaces, and by proteinase 3 in neutrophils. The name 'LL-37' derives from the two N-terminal leucines and the 37-residue length.

See the full LL-37 research profile for the complete mechanism summary, history, study citations, and references.

Practical considerations

Short plasma half-life does not necessarily mean short duration of biological effect. Many peptides — including BPC-157, GHK-Cu, and the thymosin-derived compounds — exhibit tissue retention or mechanistic effects (gene expression, signalling cascades) that outlast plasma exposure by hours to days. The pharmacological half-life and the biological-effect half-life are distinct parameters that must both be specified in any rigorous research design. Repeated-dose protocols should account for accumulation only where tissue half-life is genuinely long; for most peptides with short plasma half-life and rapid degradation, accumulation is not a practical concern.

For dose ranges in published research, see the dosing reference page. For reconstitution guidance, see the reconstitution reference page.