Subcutaneous injection (revision 8)

Subcutaneous injection delivers a substance into the adipose layer beneath the dermis. Absorption from this compartment is slower and more sustained than from muscle, because the tissue is less vascular, and it is the route used for almost every peptide therapeutic that is not given orally.^[1]

The route suits peptides for two reasons. Absorption is largely by capillary and lymphatic uptake, which handles large molecules that would be destroyed in the gut; and the depot behaviour of the tissue smooths the concentration profile, which is desirable for a drug intended to act over days.^[2]

Absorption rate varies with site, with depth, with local blood flow and with the physicochemical properties of the injected material. For an albumin-binding peptide with a half-life of days these variations are negligible against the dosing interval; for a short-acting preparation they are not.^[2]

The subcutaneous layer lies between the dermis and the muscle fascia, and its thickness varies greatly by site and by individual — from a few millimetres to several centimetres. Needle length is chosen so that the tip reaches this layer without passing into muscle, which is why short needles of 4–8 mm are used in current practice.^[1]

Injection into muscle rather than fat accelerates absorption, sometimes substantially. For insulin this is a well-documented cause of unexpected hypoglycaemia; for long-acting peptides the consequence is smaller because the absorption step is not rate-limiting.

Volume is limited by the compliance of the tissue. More than about 1.5 mL at one site produces discomfort and a visible bleb, and larger volumes are split. Peptide doses in this field are usually well under that, since a few milligrams of peptide occupy a very small volume at ordinary reconstitution concentrations.^[2][3]