An incremental method for the study of the absorption of drugs whose kinetics are described by a two-compartment model: Estimation of the microscopic rate constants

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Abstract
A method is proposed for estimating the overall absorption kinetics of drugs (expressed as percent of total amount absorbed versus time) from plasma data. It is applicable to the study of drugs whose kinetics can be described by linear one- or two- compartment models. Use is made of an iterative process based on the differential equations of the model and on linear interpolation of plasma data. The method does not require that the overall absorption kinetics should be apparent first-order and/or that the model parameters should be estimated from a previous experiment. It was tested for the influence of data scatter: added noise (CV= 10%) resulted in a variability of percent absorbed versus time of the same order of magnitude. During the calculations, the microscopic rate constants are estimated and optimalized. Data scatter resulted in wide variations in the estimates of the two-compartment model parameters. However, when a sufficiently large number of plasma concentration-time curves were studied, an average model could be determined with a reasonable precision. Model kinetics calculated from the related parameter estimates were in agreement with the theory. The method permits the exploitation of the various plasma concentration-time curves which are available after the development of an orally administered drug.