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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25453

Title: Physiologically-based Pharmacokinetic (PBPK) Models for the Description of Sequential Metabolism of Codeine to Morphine and Morphine 3-Glucuronide (M3G) in Man and Rat
Authors: Chen, Shu
Advisor: Pang, K. Sandy
Department: Pharmaceutical Sciences
Keywords: Pharmacokinetics
Physiologically- based pharmacokinetic modeling
Sequential metabolism
codeine
Issue Date: 16-Dec-2010
Abstract: Whole-body PBPK models were developed based on both the intestinal traditional model (TM) and segregated-flow model (SFM) to describe codeine sequential metabolism in man/rat. Model parameters were optimized with Scientist® and Simcyp® simulator to predict literature data after oral (p.o.) and intravenous (i.v.) codeine administration in man/rat. In vivo codeine PK studies on rats were performed to provide more data for simulation. The role of fm’ (fractional formation clearance of morphine from codeine) in model discrimination between the TM and SFM was investigated. A greater difference between the [AUC_M3G/AUC_Morphine]p.o. and [AUC_M3G/AUC_Morphine]i.v. ratio existed for the SFM, especially when the fm’ was low. It was found that our tailor-made PBPK models using Scientist® were superior to those from Simcyp® in describing codeine sequential metabolism. Residual sum of squares and AUC’s were calculated for each model, which demonstrated superiority of the SFM over TM in predicting codeine sequential metabolism in man/rat.
URI: http://hdl.handle.net/1807/25453
Appears in Collections:Master
Leslie L. Dan Faculty of Pharmacy - Master theses

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