ZeroorderAbsorption

Zero-order absorption refers to a drug absorption process in which the amount of drug entering systemic circulation per unit time remains constant, regardless of the drug concentration at the absorption site. This contrasts with first-order absorption, where the rate depends on the available amount of drug at the absorption site.

Zero-order absorption can occur when the absorption mechanism becomes saturated or when a delivery system is designed to release drug at a constant rate. It is most commonly associated with controlled-release formulations and some transdermal patches or implanted devices, where a steady input to the bloodstream is intended.

Pharmacokinetic modeling of zero-order absorption often uses an input rate constant k0. In a simple one-compartment model with zero-order input and first-order elimination, the amount in the body X(t) follows dX/dt = k0 − ke·X/V, where ke is the elimination rate constant and V is the apparent volume of distribution. With initial condition X(0)=0, the concentration during the absorption phase can be described by C(t) = (k0/(ke·V))·(1 − e^(-ke·t)); after the absorption phase ends (when the supply is exhausted), elimination governs the decline.

Clinical implications include a more predictable and smoother rise in plasma concentration, which can improve exposure consistency and reduce peak–trough fluctuations. However, once the administered dose is exhausted, input ceases and concentrations fall by elimination. True zero-order absorption is uncommon with oral dosing but can be approximated by certain controlled-release systems and many transdermal patches.

Examples include some transdermal nicotine or fentanyl patches and other delivery systems designed to maintain a near-constant input rate.