Whole-body PBPK model of alfentanil
This repository contains:
- a PK-Sim snapshot (*.json) file of the current PBPK model
- static content (e.g. text blocks, *.md files) as inputs for an evaluation plan
- an evaluation plan (evaluation-plan.json) to create an evaluation report using the snapshot and static text blocks to display the performance of the model
The latest release of the snapshot of the model, the evaluation plan and the static content can be found here.
The latest release of the PK-Sim project model file and the respective evaluation report can be found here.
This alfentanil model is intended to be used as victim drug in CYP3A4-mediated drug-drug interactions (DDI) as well as for pediatric translations with regard to CYP3A4 ontogeny.
This whole-body PBPK model of alfentanil has been developed using in particular published pharmacokinetic clinical data by Ferrier et al. 1985 [1], Kharasch et al. 1997 [2], 2004 [3], 2011 [4] , [5] as well as Meistelmann et al. 1987 [6] and Phimmasone et al. 2001 [7]. The model has then been evaluated simulating a large number of clinical studies and comparing with respective observed data.
The presented model represents an update of the alfentanil model presented by Hanke et al. [8]. Additionally, a decrease in the permeability between the intracellular and interstitial space (parameters "P (intracellular->interstitial)" and "P (interstitial->intracellular)") in intestinal mucosa was introduced to optimize quantitatively the extent of CYP3A4 gut wall metabolism and enable a proper simulation of orally absorbed alfentanil.
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The model code is distributed under the GPLv2 License.