Modelling the Double Peak Phenomenon in pharmacokinetics.

Two methods of modelling the Double Peak Phenomenon in pharmacokinetics are described; both are based on compartmental models. The first method assumes that the absorption of the drug from the gut to the systemic plasma varies with the location of the drug in the gut, with negligible absorption through the jejunum. It has the advantage of clear physiological interpretation, but there are a comparatively large number of parameters to be estimated.

On the volume of distribution at steady state and its relationship with two-compartmental models.

The volume of distribution at steady state is considered to be one of the primary pharmacokinetic measurements obtained from in vivo experiments. This quantity is quite commonly calculated using moments of the observed concentration curve, the process being referred to as noncompartmental analysis. In this paper the underlying assumptions of noncompartmental analysis are analysed with regard to the observed behaviour of models with two compartments: one of which has elimination from the central compartment, the other from the peripheral tissue compartment.

Prediction of in vivo tissue distribution from in vitro data. 2. Influence of albumin diffusion from tissue pieces during an in vitro incubation on estimated tissue-to-unbound plasma partition coefficients (Kpu).

Purpose: To determine the extent of albumin diffusion from tissue pieces into medium during in vitro incubations, to develop and assess the utility of mathematical models describing this effect on the estimation of tissue-to-unbound plasma partition coefficients (Kpu) of drug substances and to derive factors to correct for associated errors.

Methods: Twelve separate tissues were obtained from rats sacrificed by cervical dislocation, 48 h after an intravenous dose of 125I-human albumin, and tissue pieces incubated to determine the efflux of albumin into media over 2 to 4 h. A mathematical model was developed to predict and correct for the effect of albumin diffusion on the measured Kpu values of drugs.