Absorption model based on transport physics theory applied to paracetamol

Absorption of orally administered drugs from the GI tract is an important determinant of the onset of the drug effect. Models of drug absorption are frequently based on a direct or a delayed first‐order rate process. In practice, the use of the first‐order approach to predict plasma concentrations frequently yields a considerable mismatch between predicted and measured concentration profiles, particularly for the upswing of the plasma concentration after oral administration. In this investigation an alternative model, based on the advection‐dispersion equation describing the transport of chemicals through a one‐dimensional transport medium is evaluated for describing the absorption rate. It is shown that for a specific set of initial and boundary conditions the solution of the advection‐dispersion equation is similar to the Inverse Gaussian Density (IGD) input function. The latter is occasionally used to describe the absorption rate as a function of time based on two parameters, the transport velocity and the dispersion coefficient. The IGD input function was combined with a one‐compartment PK model with first‐order elimination to describe normal, accelerated, and delayed absorption of paracetamol in a 22yr old man after oral administration. A comparison of the model fit with results obtained on the basis of a first‐order absorption model demonstrate that the IGD function is more accurate in describing the PK curve after oral administration. Clinical Pharmacology & Therapeutics (2004) 75 , P80–P80; doi: 10.1016/j.clpt.2003.11.307