Figure 8.

The reasoning behind the assumptions regarding the absorption rate of subcutaneous hydrocortisone (HC) administration. This rate depends on the subcutaneous dose magnitude, and the within-subject change in absorption rate with time. HC is a lipophilic molecule; its diffusion is hardly restricted by tissue membranes and thus can be assumed to be isotropic. Accordingly, we used a sphere as an approximation of the shape and movement of hormonal molecules infused into the subcutaneous tissue. Left: the higher the subcutaneous dose volume, the lower the absorption rate k_α (k_α is inversely proportional to the cubic root of the dose volume). When a small dose is administered by the pump cannula (e.g., 30 μL or 0.3 mg of HC) (a), the ratio of the area of the sphere to its volume is approximately 2.4-times greater than when a 13-times larger dose is administered (e.g., 400 μL or 4 mg of HC) (b). Therefore, the absorption rate drops to almost a similar degree (from about 0.01 to about 0.004). When administered in high doses, an increased fat deposition of the hormone could also contribute to dose-dependent changes in the absorption rate. Right: compared to the state where the absorption rate was considered constant and independent of the dosage, our assumption (of a dose-dependent k_α) indicates that in lower doses, the absorption would be higher, while in higher doses would be lower (c). Part of the Figure has been created with BioRender.com.