Журнал биоэквивалентности и биодоступности

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Modelling the Double Peak Phenomenon

Keith R. Godfrey, Arundel PA, Zhu W, Dong Z and Bryant R

Multiple peaking in concentration-time profiles following the administration of a single dose of a drug has been the subject of considerable interest recently. Two methods of modelling the phenomenon of Double Peaks in pharmacokinetics, both based on compartmental models were described in a recent paper. The first method, the Variability of Absorption approach, 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 and constant (but not necessarily the same) absorption rates in the duodenum and the ileum. The second method, the Parallel Inputs approach, assumes simultaneous input via two parallel pathways. In the present paper the emphasis is on improved fitting of the tail-end of the profiles for both approaches, especially at low plasma concentrations, by use of different forms of data weighting, or alternatively by introducing more complexity in their distribution models. The two modelling approaches are used to model four data sets from the literature with the measurement in each case being concentration of drug in the systemic plasma following a single oral dose of the drug, either in solution form or as an emulsion.