Whole-body PBPK model of clarithromycin.

The latest release of this model including a report on model building, model features and model evaluation 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.