This process—known as first-pass metabolism—is often essential. It protects the body from toxins, controls absorption rate, and transforms compounds into active or inactive forms. But it also creates challenges. In some cases, the liver rapidly breaks down beneficial compounds before they can act, leading to poor bioavailability.
By delivering nutrients or drugs through the skin, directly into the bloodstream, we can avoid hepatic filtration and achieve higher plasma levels from smaller doses. This is particularly useful for compounds that are heavily degraded or poorly absorbed in the gut. It also circumvents variability caused by digestive conditions or food interactions.
However, bypassing the liver means we lose its natural role in moderating release and generating certain metabolites. A key part of our research is designing delivery systems that recreate the strengths of oral routes—such as steady uptake—without their downsides. This includes slowing absorption through formulation viscosity, occlusion, or skin impedance modulation, avoiding sharp spikes in blood levels.
Different routes can yield different metabolic profiles. Some drugs require liver enzymes to become active; others become toxic when transformed. Understanding these differences is critical in transdermal system design.
Our feasibility studies aim to map out these trade-offs, exploring whether higher unmetabolised concentrations deliver greater benefit—or whether a drug’s efficacy depends on hepatic transformation.
We are currently testing the pharmacokinetic behaviour of different transdermal carriers using synthetic and ex vivo models. By analysing rate of absorption and metabolite presence under various conditions, we hope to inform better decisions around route of delivery for cases where oral administration is compromised or contraindicated.