Drug-Drug Interactions Pharmacokinetic Models with Extravascular Administration: Estimation of Elimination and Absorption Rate Constants

Abstract

One and two-compartment pharmacokinetic models with drug-drug interactions are proposed. Two drugs are given orally simultaneously, so that their interaction affects the drug absorption process and subsequently the elimination process. The aim of this paper is to estimate the elimination and absorption rate constants by evaluating the data set of time and drug concentration. This data set was divided into two time phases: large-time elimination phase to estimate the elimination rate constant, and small-time absorption phase to estimate the absorption rate constant. Since the models are nonlinear, the Taylor expansion is employed to so that the Wagner-Nelson and the Loo-Riegelman methods can be used for estimation. Finally, simulations were performed using the generated arbitrary data set of time and concentration, instead of an actual data set, to derive the solution of drug concentration concerning time numerically. In these simulations we compared the original parameter values with their estimates for the one and two-compartment models, and we concluded that the two-compartment model produced better estimates than the one-compartment model. Qualitatively, the two-compartment model gives smaller drug concentration curve deviations between the original and the estimated curve compared with the one-compartment model.

Keywords

• pharmacokinetics
• drug-drug interactions
• parameter estimation
• wagner-nelson
• loo-riegelman.