Whole-body PBPK model of clarithromycin.

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.

Clarithromycin is a widely prescribed macrolide antibiotic and a substrate and mechanism-based inactivator of CYP3A4. Furthermore, clarithromycin is a substrate and inhibitor of P-gp and an inhibitor of OATP1B1 and OATP1B3. Clarithromycin has been proposed as one of the best alternative CYP3A4 inhibitors for clinical DDI studies to avoid further use of ketoconazole.

A whole-body PBPK model for clarithromycin was developed including its metabolism by CYP3A4 and its mechanism-based inactivation of the respective enzyme as well as its inhibition of P-gp.

The presented clarithromycin model was developed by Moj et al. [1] and revised by Hanke et al. [2].

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The model code is distributed under the GPLv2 License.

[1] Moj D, Hanke N, Britz H, Frechen S, Kanacher T, Wendl T, Haefeli WE, Lehr T. Clarithromycin, Midazolam, and Digoxin: Application of PBPK Modeling to Gain New Insights into Drug-Drug Interactions and Co-medication Regimens. AAPS J. 2017 Jan;19(1):298-312.

[2] Hanke N, Frechen S, Moj D, Britz H, Eissing T, Wendl T, Lehr T. PBPK models for CYP3A4 and P-gp DDI prediction: a modeling network of rifampicin, itraconazole, clarithromycin, midazolam, alfentanil and digoxin. CPT Pharmacometrics Syst Pharmacol. 2018 Oct;7(10):647-659.